---
DOAJ_listed: '1'
OA_place: publisher
OA_type: gold
PlanS_conform: '1'
_id: '21245'
abstract:
- lang: eng
text: Flickering light is a new promising, fully non-invasive brain stimulation
technique that utilizes intermittent sensory stimulation to induce brainwave synchronization
(entrainment). While the effects of 40 Hz externally induced neural entrainment
have been extensively described, little is known about 60 Hz entrainment in humans.
This study presents preliminary observations on the neural and somatic response
to flickering 60 Hz light in healthy volunteers over a 3-week period. Fourteen
volunteers were randomized to receive either 60 Hz flickering white light or constant
light as sham (30-min sessions, 3 weeks, 5 days/week on weekdays). Neural entrainment
was assessed with EEG on days 1, 5 and 19. Salivary cortisol and C-reactive protein
(CRP) levels, measured with ELISA, assessed the somatic response to stimulation.
Side effects and well-being were monitored via questionnaires. EEG recordings
showed neural entrainment and synchrony in response to 60 Hz flickering light
across multiple cortical regions, including occipital, central, temporal, and
frontal areas. The entrainment power and synchronization between different cortical
regions declined significantly by day 19 compared to day 1, indicating possible
neural habituation. Cortisol and CRP salivary levels were unchanged, and minor
side effects were reported with equal frequency in the active and sham groups.
Our findings show that 60 Hz flickering light can induce significant neural entrainment
and synchrony in healthy adults and is well tolerated. The decline in entrainment
strength and neural synchrony observed with repeated 60 Hz stimulations suggests
plastic changes in the cortex. To the best of our knowledge, this is the first
study to characterize neural and somatic responses to repeated 60 Hz flickering
visual stimuli. Given the well-known connection between 60 Hz brain oscillations
and cognition, neuroplasticity, and their role in neuropsychiatric disorders,
additional research in both preclinical and clinical settings is warranted.
acknowledgement: This study was funded by Syntropic Medical and supported by an Austria
Wirtschaftsservice (AWS) grant (grant number P2414247 to Syntropic Medical). Syntropic
Medical employees were involved in study design, data collection and analysis, decision
to publish, and preparation of the manuscript. AWS had no role in study design,
data collection and analysis, decision to publish, or preparation of the manuscript.
article_number: e0332310
article_processing_charge: Yes
article_type: original
author:
- first_name: MohammadAmin
full_name: Alamalhoda, MohammadAmin
last_name: Alamalhoda
- first_name: Friederike
full_name: Leesch, Friederike
last_name: Leesch
- first_name: Francesca
full_name: Giovanetti, Francesca
last_name: Giovanetti
- first_name: Eoghan
full_name: Dunne, Eoghan
last_name: Dunne
- first_name: Giuseppina
full_name: Pilloni, Giuseppina
last_name: Pilloni
- first_name: Mark
full_name: Caffrey, Mark
last_name: Caffrey
- first_name: Jack
full_name: O’Keeffe, Jack
last_name: O’Keeffe
- first_name: Alessandro
full_name: Venturino, Alessandro
id: 41CB84B2-F248-11E8-B48F-1D18A9856A87
last_name: Venturino
orcid: 0000-0003-2356-9403
- first_name: Maria Teresa
full_name: Ferretti, Maria Teresa
last_name: Ferretti
citation:
ama: Alamalhoda M, Leesch F, Giovanetti F, et al. Exploring neural entrainment and
synchrony in response to repeated 60 Hz flickering white light in healthy volunteers.
PLOS One. 2025;20(10). doi:10.1371/journal.pone.0332310
apa: Alamalhoda, M., Leesch, F., Giovanetti, F., Dunne, E., Pilloni, G., Caffrey,
M., … Ferretti, M. T. (2025). Exploring neural entrainment and synchrony in response
to repeated 60 Hz flickering white light in healthy volunteers. PLOS One.
Public Library of Science. https://doi.org/10.1371/journal.pone.0332310
chicago: Alamalhoda, MohammadAmin, Friederike Leesch, Francesca Giovanetti, Eoghan
Dunne, Giuseppina Pilloni, Mark Caffrey, Jack O’Keeffe, Alessandro Venturino,
and Maria Teresa Ferretti. “Exploring Neural Entrainment and Synchrony in Response
to Repeated 60 Hz Flickering White Light in Healthy Volunteers.” PLOS One.
Public Library of Science, 2025. https://doi.org/10.1371/journal.pone.0332310.
ieee: M. Alamalhoda et al., “Exploring neural entrainment and synchrony in
response to repeated 60 Hz flickering white light in healthy volunteers,” PLOS
One, vol. 20, no. 10. Public Library of Science, 2025.
ista: Alamalhoda M, Leesch F, Giovanetti F, Dunne E, Pilloni G, Caffrey M, O’Keeffe
J, Venturino A, Ferretti MT. 2025. Exploring neural entrainment and synchrony
in response to repeated 60 Hz flickering white light in healthy volunteers. PLOS
One. 20(10), e0332310.
mla: Alamalhoda, MohammadAmin, et al. “Exploring Neural Entrainment and Synchrony
in Response to Repeated 60 Hz Flickering White Light in Healthy Volunteers.” PLOS
One, vol. 20, no. 10, e0332310, Public Library of Science, 2025, doi:10.1371/journal.pone.0332310.
short: M. Alamalhoda, F. Leesch, F. Giovanetti, E. Dunne, G. Pilloni, M. Caffrey,
J. O’Keeffe, A. Venturino, M.T. Ferretti, PLOS One 20 (2025).
date_created: 2026-02-16T15:29:26Z
date_published: 2025-10-07T00:00:00Z
date_updated: 2026-02-17T12:19:15Z
day: '07'
ddc:
- '570'
department:
- _id: SaSi
doi: 10.1371/journal.pone.0332310
external_id:
pmid:
- '41056352 '
file:
- access_level: open_access
checksum: 22a4e92a733152633c4553f107f66765
content_type: application/pdf
creator: dernst
date_created: 2026-02-17T12:16:18Z
date_updated: 2026-02-17T12:16:18Z
file_id: '21301'
file_name: 2025_PlosOne_Alamalhoda.pdf
file_size: 1388424
relation: main_file
success: 1
file_date_updated: 2026-02-17T12:16:18Z
has_accepted_license: '1'
intvolume: ' 20'
issue: '10'
language:
- iso: eng
license: https://creativecommons.org/licenses/by/4.0/
month: '10'
oa: 1
oa_version: Published Version
pmid: 1
publication: PLOS One
publication_identifier:
eissn:
- 1932-6203
publication_status: published
publisher: Public Library of Science
quality_controlled: '1'
related_material:
link:
- relation: software
url: https://github.com/AminAlam/HVS
status: public
title: Exploring neural entrainment and synchrony in response to repeated 60 Hz flickering
white light in healthy volunteers
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 20
year: '2025'
...
---
APC_amount: 2236,02 EUR
DOAJ_listed: '1'
OA_place: publisher
OA_type: gold
_id: '19566'
abstract:
- lang: eng
text: "Purpose: Optic nerve crush (ONC) is a model for studying optic nerve trauma.
Unilateral ONC induces massive retinal ganglion cell (RGC) degeneration in the
affected eye, leading to vision loss within a month. A common assumption has been
that the non-injured contralateral eye is unaffected due to the minimal retino-retinal
projections of the RGCs at the chiasm. Yet, recently, microglia, the brain-resident
macrophages, have shown a responsive phenotype in the contralateral eye after
ONC. Whether RGC loss accompanies this phenotype is still controversial.\r\n\r\nMethods:
Using the available RGCode algorithm and developing our own RGC-Quant deep-learning-based
tool, we quantify RGC's total number and density across the entire retina after
ONC.\r\n\r\nResults: We confirm a short-term microglia response in the contralateral
eye after ONC, but this did not affect the microglia number. Furthermore, we cannot
confirm the previously reported RGC loss between naïve and contralateral retinas
5 weeks after ONC induction across the commonly used Cx3cr1creERT2 and C57BL6/J
mouse models. Neither sex nor the direct comparison of the RGC markers Brn3a and
RBPMS, with Brn3a co-labeling, on average, 89% of the RBPMS+-cells, explained
this discrepancy, suggesting that the early microglia-responsive phenotype does
not have immediate consequences on the RGC number.\r\n\r\nConclusions: Our results
corroborate that unilateral optic nerve injury elicits a microglial response in
the uninjured contralateral eye but without RGC loss. Therefore, the contralateral
eye should be treated separately and not as an ONC control."
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: PreCl
acknowledgement: "The authors thank the Scientific Service Units (SSU) of ISTA for
the provided resources, specifically the Imaging and Optics Facility (IOF), the
Lab Support Facility (LSF), and the Pre-Clinical Facility (PCF) team, specifically
Sonja Haslinger, Claudia Gold, and Michael Schunn, for mouse colony management and
support. We thank all members of the Siegert group for constant feedback on the
project and the manuscript. \r\nSupported in whole or in part by the Austrian Science
Fund (FWF) [10.55776/P37131]. For open access purposes, the author has applied a
CC BY public copyright license to any author-accepted manuscript version arising
from this submission. "
article_number: '49'
article_processing_charge: Yes
article_type: original
author:
- first_name: Florianne E
full_name: Schoot Uiterkamp, Florianne E
id: 3526230C-F248-11E8-B48F-1D18A9856A87
last_name: Schoot Uiterkamp
- first_name: Margaret E
full_name: Maes, Margaret E
id: 3838F452-F248-11E8-B48F-1D18A9856A87
last_name: Maes
orcid: 0000-0001-9642-1085
- first_name: Mohammad
full_name: Alamalhoda, Mohammad
last_name: Alamalhoda
- first_name: Arsalan
full_name: Firoozi, Arsalan
last_name: Firoozi
- first_name: Gloria
full_name: Colombo, Gloria
id: 3483CF6C-F248-11E8-B48F-1D18A9856A87
last_name: Colombo
orcid: 0000-0001-9434-8902
- first_name: Sandra
full_name: Siegert, Sandra
id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
last_name: Siegert
orcid: 0000-0001-8635-0877
citation:
ama: Miteva FE, Maes ME, Alamalhoda M, Firoozi A, Colombo G, Siegert S. Optic nerve
crush does not induce retinal ganglion cell loss in the contralateral eye. Investigative
Ophthalmology & Visual Science. 2025;66(3). doi:10.1167/iovs.66.3.49
apa: Miteva, F. E., Maes, M. E., Alamalhoda, M., Firoozi, A., Colombo, G., &
Siegert, S. (2025). Optic nerve crush does not induce retinal ganglion cell loss
in the contralateral eye. Investigative Ophthalmology & Visual Science.
Association for Research in Vision and Ophthalmology. https://doi.org/10.1167/iovs.66.3.49
chicago: Miteva, Florianne E, Margaret E Maes, Mohammad Alamalhoda, Arsalan Firoozi,
Gloria Colombo, and Sandra Siegert. “Optic Nerve Crush Does Not Induce Retinal
Ganglion Cell Loss in the Contralateral Eye.” Investigative Ophthalmology &
Visual Science. Association for Research in Vision and Ophthalmology, 2025.
https://doi.org/10.1167/iovs.66.3.49.
ieee: F. E. Miteva, M. E. Maes, M. Alamalhoda, A. Firoozi, G. Colombo, and S. Siegert,
“Optic nerve crush does not induce retinal ganglion cell loss in the contralateral
eye,” Investigative Ophthalmology & Visual Science, vol. 66, no. 3.
Association for Research in Vision and Ophthalmology, 2025.
ista: Miteva FE, Maes ME, Alamalhoda M, Firoozi A, Colombo G, Siegert S. 2025. Optic
nerve crush does not induce retinal ganglion cell loss in the contralateral eye.
Investigative Ophthalmology & Visual Science. 66(3), 49.
mla: Miteva, Florianne E., et al. “Optic Nerve Crush Does Not Induce Retinal Ganglion
Cell Loss in the Contralateral Eye.” Investigative Ophthalmology & Visual
Science, vol. 66, no. 3, 49, Association for Research in Vision and Ophthalmology,
2025, doi:10.1167/iovs.66.3.49.
short: F.E. Miteva, M.E. Maes, M. Alamalhoda, A. Firoozi, G. Colombo, S. Siegert,
Investigative Ophthalmology & Visual Science 66 (2025).
corr_author: '1'
date_created: 2025-04-15T13:40:35Z
date_published: 2025-03-01T00:00:00Z
date_updated: 2026-05-20T06:37:12Z
day: '01'
ddc:
- '570'
department:
- _id: SaSi
doi: 10.1167/iovs.66.3.49
external_id:
pmid:
- '40126507'
file:
- access_level: open_access
checksum: e8722ce5792f6c08fe1e191f7de6f147
content_type: application/pdf
creator: dernst
date_created: 2025-04-15T13:49:10Z
date_updated: 2025-04-15T13:49:10Z
file_id: '19567'
file_name: 2025_IOVS_SchootUiterkamp.pdf
file_size: 2721477
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success: 1
file_date_updated: 2025-04-15T13:49:10Z
has_accepted_license: '1'
intvolume: ' 66'
issue: '3'
language:
- iso: eng
month: '03'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 7be82147-9f16-11ee-852c-f44682d73140
grant_number: P37131
name: Dissecting the morpho-functional relationship of microglia
- _id: 3AC91DDA-15DF-11EA-824D-93A3E7B544D1
call_identifier: FWF
name: FWF Open Access Fund
publication: Investigative Ophthalmology & Visual Science
publication_identifier:
issn:
- 1552-5783
publication_status: published
publisher: Association for Research in Vision and Ophthalmology
quality_controlled: '1'
related_material:
link:
- relation: software
url: https://github.com/siegert-lab/RGC-Quant
record:
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relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: Optic nerve crush does not induce retinal ganglion cell loss in the contralateral
eye
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 66
year: '2025'
...
---
APC_amount: 3948 EUR
DOAJ_listed: '1'
OA_place: publisher
OA_type: gold
PlanS_conform: '1'
_id: '19593'
abstract:
- lang: eng
text: Prenatal immune challenges pose significant risks to human embryonic brain
and eye development. However, our knowledge about the safe usage of anti-inflammatory
drugs during pregnancy is still limited. While human induced pluripotent stem
cells (hIPSC)-derived brain organoid models have started to explore functional
consequences upon viral stimulation, these models commonly lack microglia, which
are susceptible to and promote inflammation. Furthermore, microglia are actively
involved in neuronal development. Here, we generate hIPSC-derived microglia precursor
cells and assemble them into retinal organoids. Once the outer plexiform layer
forms, these hIPSC-derived microglia (iMG) fully integrate into the retinal organoids.
Since the ganglion cell survival declines by this time in 3D-retinal organoids,
we adapted the model into 2D and identify that the improved ganglion cell number
significantly decreases only with iMG presence. In parallel, we applied the immunostimulant
POLY(I:C) to mimic a fetal viral infection. While POLY(I:C) exposure alters the
iMG phenotype, it does not hinder their interaction with ganglion cells. Furthermore,
iMG significantly enhance the supernatant’s inflammatory secretome and increase
retinal cell proliferation. Simultaneous exposure with the non-steroidal anti-inflammatory
drug (NSAID) ibuprofen dampens POLY(I:C)-mediated changes of the iMG phenotype
and ameliorates cell proliferation. Remarkably, while POLY(I:C) disrupts neuronal
calcium dynamics independent of iMG, ibuprofen rescues this effect only if iMG
are present. Mechanistically, ibuprofen targets the enzymes cyclooxygenase 1 and
2 (COX1/PTGS1 and COX2/PTGS2) simultaneously, from which iMG mainly express COX1.
Selective COX1 blockage fails to restore the calcium peak amplitude upon POLY(I:C)
stimulation, suggesting ibuprofen’s beneficial effect depends on the presence
and interplay of COX1 and COX2. These findings underscore the importance of microglia
in the context of prenatal immune challenges and provide insight into the mechanisms
by which ibuprofen exerts its protective effects during embryonic development.
acknowledged_ssus:
- _id: LifeSc
- _id: Bio
acknowledgement: We thank the scientific service units at ISTA, specifically the Lab
Support Facility (LSF), the Molecular Biology Services/Virus Services Team, specifically
Flavia Gama Gomes Leite and Mark Andrew Smyth, for the virus production, and the
Imaging and Optics Facility (IOF). We thank all members of the Siegert group and
Marco Benevento for their constant feedback on the project and comments on the manuscript.
A special thanks to Rouven Schulz for input on statistical analysis and sharing
R-scripts, Gloria Colombo for the introduction to cell sorting, Negar Vehdani and
Florianne Schoot Uiterkamp for their support in cell culture. This research was
supported by the Gesellschaft für Forschungsförderung Niederösterreich (grant No.
Sc19-017 to V.H.).
article_number: '98'
article_processing_charge: Yes
article_type: original
author:
- first_name: Verena
full_name: Hübschmann, Verena
id: 32B7C918-F248-11E8-B48F-1D18A9856A87
last_name: Hübschmann
- first_name: Medina
full_name: Korkut, Medina
id: 4B51CE74-F248-11E8-B48F-1D18A9856A87
last_name: Korkut
orcid: 0000-0003-4309-2251
- first_name: Alessandro
full_name: Venturino, Alessandro
id: 41CB84B2-F248-11E8-B48F-1D18A9856A87
last_name: Venturino
orcid: 0000-0003-2356-9403
- first_name: Juan Pablo
full_name: Maya-Arteaga, Juan Pablo
id: c815d433-1f5d-11f0-a875-dad18b1e5924
last_name: Maya-Arteaga
- first_name: Sandra
full_name: Siegert, Sandra
id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
last_name: Siegert
orcid: 0000-0001-8635-0877
citation:
ama: Schmied V, Korkut M, Venturino A, Maya-Arteaga JP, Siegert S. Microglia determine
an immune-challenged environment and facilitate ibuprofen action in human retinal
organoids. Journal of Neuroinflammation. 2025;22(1). doi:10.1186/s12974-025-03366-x
apa: Schmied, V., Korkut, M., Venturino, A., Maya-Arteaga, J. P., & Siegert,
S. (2025). Microglia determine an immune-challenged environment and facilitate
ibuprofen action in human retinal organoids. Journal of Neuroinflammation.
Springer Nature. https://doi.org/10.1186/s12974-025-03366-x
chicago: Schmied, Verena, Medina Korkut, Alessandro Venturino, Juan Pablo Maya-Arteaga,
and Sandra Siegert. “Microglia Determine an Immune-Challenged Environment and
Facilitate Ibuprofen Action in Human Retinal Organoids.” Journal of Neuroinflammation.
Springer Nature, 2025. https://doi.org/10.1186/s12974-025-03366-x.
ieee: V. Schmied, M. Korkut, A. Venturino, J. P. Maya-Arteaga, and S. Siegert, “Microglia
determine an immune-challenged environment and facilitate ibuprofen action in
human retinal organoids,” Journal of Neuroinflammation, vol. 22, no. 1.
Springer Nature, 2025.
ista: Schmied V, Korkut M, Venturino A, Maya-Arteaga JP, Siegert S. 2025. Microglia
determine an immune-challenged environment and facilitate ibuprofen action in
human retinal organoids. Journal of Neuroinflammation. 22(1), 98.
mla: Schmied, Verena, et al. “Microglia Determine an Immune-Challenged Environment
and Facilitate Ibuprofen Action in Human Retinal Organoids.” Journal of Neuroinflammation,
vol. 22, no. 1, 98, Springer Nature, 2025, doi:10.1186/s12974-025-03366-x.
short: V. Schmied, M. Korkut, A. Venturino, J.P. Maya-Arteaga, S. Siegert, Journal
of Neuroinflammation 22 (2025).
corr_author: '1'
date_created: 2025-04-20T22:01:28Z
date_published: 2025-04-03T00:00:00Z
date_updated: 2026-05-06T12:49:37Z
day: '03'
ddc:
- '570'
department:
- _id: SaSi
doi: 10.1186/s12974-025-03366-x
external_id:
isi:
- '001459311800002'
pmid:
- '40181459'
file:
- access_level: open_access
checksum: dcc355c21ab713e45fda5c61b5fa5299
content_type: application/pdf
creator: dernst
date_created: 2025-04-22T09:46:27Z
date_updated: 2025-04-22T09:46:27Z
file_id: '19607'
file_name: 2025_JourNeuroinflammation_Schmied.pdf
file_size: 4482167
relation: main_file
success: 1
file_date_updated: 2025-04-22T09:46:27Z
has_accepted_license: '1'
intvolume: ' 22'
isi: 1
issue: '1'
language:
- iso: eng
month: '04'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 9B99D380-BA93-11EA-9121-9846C619BF3A
grant_number: SC19-017
name: How human microglia shape developing neurons during health and inflammation
- _id: B67AFEDC-15C9-11EA-A837-991A96BB2854
name: IST Austria Open Access Fund
publication: Journal of Neuroinflammation
publication_identifier:
eissn:
- 1742-2094
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
link:
- description: News on ISTA website
relation: press_release
url: https://ista.ac.at/en/news/pink-skies/
record:
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relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: Microglia determine an immune-challenged environment and facilitate ibuprofen
action in human retinal organoids
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 22
year: '2025'
...
---
OA_place: publisher
_id: '20074'
abstract:
- lang: eng
text: "Prenatal immune challenges pose significant risks to human embryonic brain
and eye development. However, we still lack knowledge about the safe usage of
anti-inflammatory drugs during pregnancy. Human induced pluripotent stem cell
(hIPSC)-derived brain organoid models provide a unique opportunity to investigate
neuronal development and have started to explore functional consequences upon
viral infection. However, brain organoids usually lack microglia, the brain-resident
immune cells. They are present in the early human embryonic brain and actively
participate in neuronal circuit development. At the same time, microglia are known
for their immune-sensing properties and will influence viral-mediated effects.
In my thesis, I was interested to study the multifunctional role of human microglia
during retinal development. \r\nIn chapter 1, I characterize the innate occurrence
of IBA1+-microglia-like cells within the retinal organoid differentiation (Bartalska
et al., 2022). Therefore, we differentiate hIPSC using an unguided retinal organoid
differentiation protocol and observe the presence of IBA1+-microglia-like cells
alongside retinal cups between week 3 and 4 in 2.5D culture. However, instead
of infiltrating the neuroectodermal sides, they enrich within non-pigmented, 3D-cystic
compartments that develop in low numbers parallel to 3D-retinal organoids. To
enrich for IBA1+-microglia precursors (preMG), we guided the differentiation with
a low-dosed BMP4 application, which prevents retinal cup development and enhances
microglia and 3D-cysts formation. We characterize the differentiated preMG for
their microglia-like identity and validated their functionality. In parallel,
mass spectrometry identifies the 3D-cysts to express mesenchymal and epithelial
markers. We confirm that comparable 3D-cysts are also the preferential environment
for IBA1+-microglia-like cells within the unguided retinal organoid differentiation.
\r\nIn chapter 2, I investigate how microglia influence retinal development and
whether they contribute to viral-mediated consequences (Schmied et al., 2025).
Here, we assemble preMG, which we have characterized in chapter 1, into 3D-retinal
organoids. Once the outer plexiform layer forms, microglia-like cells (iMG) populate
them and interact with retinal cell types. However, at this developmental stage,
the ganglion cell number decreases in 3D-retinal organoids. Thus, we adapted the
model into 2D which promotes their survival. Integrated iMG engulf ganglion cells
and control their cell number. In parallel, we apply the immunostimulant POLY(I:C)
to mimic a fetal viral infection. Although POLY(I:C) stimulation affects iMG phenotype,
it does not influence their interaction with ganglion cells. Furthermore, iMG
presence significantly contributes to the supernatant’s inflammatory secretome
and increases retinal cell proliferation. Simultaneous exposure to the non-steroidal
anti-inflammatory drug (NSAID) ibuprofen dampens POLY(I:C)-mediated consequences
of the iMG phenotype and ameliorates cell proliferation. Remarkably, while POLY(I:C)
disrupts neuronal calcium dynamics independent of iMG presence, ibuprofen rescues
this effect only in the presence of iMG. Mechanistically, ibuprofen blocks the
enzymes cyclooxygenase 1 and 2 (COX1/ PTGS1 and COX2/ PTGS2) simultaneously, from
which iMG predominantly express COX1. Selective inhibition of COX1 does not restore
the calcium peak amplitude upon POLY(I:C) stimulation, indicating ibuprofen’s
effect depends on the presence and interplay of both, COX1 and COX2. \r\nIn summary,
we characterized the 3D-retinal organoid model for the occurrence of IBA1+-microglia
like cells. As the innately developing IBA1+-cells enrich in mesenchymal over
retinal structures, we optimized a protocol to differentiate IBA1+-microglia precursors.
By combining these two models we generate microglia-assembled retinal organoids.
Our results underscore the importance of microglia during neurodevelopment, in
the context of prenatal immune challenges and provide insight into the mechanisms
by which ibuprofen exerts its protective effects during embryonic development."
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Verena
full_name: Hübschmann, Verena
id: 32B7C918-F248-11E8-B48F-1D18A9856A87
last_name: Hübschmann
citation:
ama: Schmied V. Human microglia impact neuronal development in retinal organoids.
2025. doi:10.15479/AT-ISTA-20074
apa: Schmied, V. (2025). Human microglia impact neuronal development in retinal
organoids. Institute of Science and Technology Austria. https://doi.org/10.15479/AT-ISTA-20074
chicago: Schmied, Verena. “ Human Microglia Impact Neuronal Development in Retinal
Organoids.” Institute of Science and Technology Austria, 2025. https://doi.org/10.15479/AT-ISTA-20074.
ieee: V. Schmied, “ Human microglia impact neuronal development in retinal organoids,”
Institute of Science and Technology Austria, 2025.
ista: Schmied V. 2025. Human microglia impact neuronal development in retinal organoids.
Institute of Science and Technology Austria.
mla: Schmied, Verena. Human Microglia Impact Neuronal Development in Retinal
Organoids. Institute of Science and Technology Austria, 2025, doi:10.15479/AT-ISTA-20074.
short: V. Schmied, Human Microglia Impact Neuronal Development in Retinal Organoids,
Institute of Science and Technology Austria, 2025.
corr_author: '1'
date_created: 2025-07-24T12:37:22Z
date_published: 2025-07-24T00:00:00Z
date_updated: 2026-05-06T12:49:36Z
day: '24'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: GradSch
- _id: SaSi
doi: 10.15479/AT-ISTA-20074
file:
- access_level: closed
checksum: d09f9984002353ad7442358394919bf3
content_type: application/x-zip-compressed
creator: vhuebsch
date_created: 2025-07-30T08:47:53Z
date_updated: 2025-07-30T08:47:53Z
file_id: '20086'
file_name: PhD_Thesis_Schmied.zip
file_size: 43566093
relation: source_file
- access_level: open_access
checksum: 4833690d7283c587f518ba98eeb2c946
content_type: application/pdf
creator: vhuebsch
date_created: 2025-07-30T08:47:46Z
date_updated: 2025-07-30T09:29:09Z
file_id: '20087'
file_name: PhD_Thesis_Schmied.pdf
file_size: 13120922
relation: main_file
file_date_updated: 2025-07-30T09:29:09Z
has_accepted_license: '1'
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
page: '151'
project:
- _id: 9B99D380-BA93-11EA-9121-9846C619BF3A
grant_number: SC19-017
name: How human microglia shape developing neurons during health and inflammation
publication_identifier:
isbn:
- 978-3-99078-060-2
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '11478'
relation: part_of_dissertation
status: public
- id: '19593'
relation: part_of_dissertation
status: public
status: public
supervisor:
- first_name: Sandra
full_name: Siegert, Sandra
id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
last_name: Siegert
orcid: 0000-0001-8635-0877
title: ' Human microglia impact neuronal development in retinal organoids'
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2025'
...
---
OA_place: publisher
_id: '20467'
acknowledged_ssus:
- _id: Bio
- _id: SSU
- _id: PreCl
- _id: LifeSc
acknowledgement: "The work presented in this Thesis was carried out at the Institute
of Science and Technology\r\nAustria (ISTA), and was supported by the Austrian Science
Fund (FWF) [10.55776/P37131].\r\nI would like to thank the Scientific Service Units
(SSU) of ISTA for the provided resources,\r\nspecifically the Imaging and Optics
Facility (IOF), the Lab Support Facility (LSF), and the\r\nPre-Clinical Facility
(PCF) team, specifically Sonja Haslinger, Claudia Gold, and Michael\r\nSchunn, for
mouse colony management and support. "
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Florianne E
full_name: Miteva, Florianne E
id: 3526230C-F248-11E8-B48F-1D18A9856A87
last_name: Miteva
citation:
ama: Miteva FE. The role of cyclooxygenase 1 on microglial response to inflammatory
stressors. 2025. doi:10.15479/AT-ISTA-20467
apa: Miteva, F. E. (2025). The role of cyclooxygenase 1 on microglial response
to inflammatory stressors. Institute of Science and Technology Austria. https://doi.org/10.15479/AT-ISTA-20467
chicago: Miteva, Florianne E. “The Role of Cyclooxygenase 1 on Microglial Response
to Inflammatory Stressors.” Institute of Science and Technology Austria, 2025.
https://doi.org/10.15479/AT-ISTA-20467.
ieee: F. E. Miteva, “The role of cyclooxygenase 1 on microglial response to inflammatory
stressors,” Institute of Science and Technology Austria, 2025.
ista: Miteva FE. 2025. The role of cyclooxygenase 1 on microglial response to inflammatory
stressors. Institute of Science and Technology Austria.
mla: Miteva, Florianne E. The Role of Cyclooxygenase 1 on Microglial Response
to Inflammatory Stressors. Institute of Science and Technology Austria, 2025,
doi:10.15479/AT-ISTA-20467.
short: F.E. Miteva, The Role of Cyclooxygenase 1 on Microglial Response to Inflammatory
Stressors, Institute of Science and Technology Austria, 2025.
corr_author: '1'
date_created: 2025-10-14T10:24:41Z
date_published: 2025-10-14T00:00:00Z
date_updated: 2026-05-20T06:37:12Z
day: '14'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: GradSch
- _id: SaSi
doi: 10.15479/AT-ISTA-20467
file:
- access_level: closed
checksum: 03537697be8c688d3a05cf948288e48f
content_type: application/pdf
creator: fschootu
date_created: 2025-10-17T11:09:11Z
date_updated: 2025-10-17T11:13:25Z
embargo: 2026-10-14
embargo_to: open_access
file_id: '20484'
file_name: 2025_Miteva_Florianne_thesis.pdf
file_size: 13668588
relation: main_file
- access_level: closed
checksum: df4930d7211cf9cfe1254b77204dc1d3
content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
creator: fschootu
date_created: 2025-10-23T11:33:06Z
date_updated: 2025-10-23T11:33:06Z
file_id: '20525'
file_name: 2025_Miteva_florianne_thesis.docx
file_size: 28991918
relation: source_file
file_date_updated: 2025-10-23T11:33:06Z
has_accepted_license: '1'
language:
- iso: eng
month: '10'
oa_version: Published Version
page: '99'
project:
- _id: 7be82147-9f16-11ee-852c-f44682d73140
grant_number: P37131
name: Dissecting the morpho-functional relationship of microglia
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '19566'
relation: part_of_dissertation
status: public
status: public
supervisor:
- first_name: Sandra
full_name: Siegert, Sandra
id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
last_name: Siegert
orcid: 0000-0001-8635-0877
title: The role of cyclooxygenase 1 on microglial response to inflammatory stressors
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2025'
...
---
OA_place: publisher
OA_type: hybrid
_id: '14257'
abstract:
- lang: eng
text: Mapping the complex and dense arrangement of cells and their connectivity
in brain tissue demands nanoscale spatial resolution imaging. Super-resolution
optical microscopy excels at visualizing specific molecules and individual cells
but fails to provide tissue context. Here we developed Comprehensive Analysis
of Tissues across Scales (CATS), a technology to densely map brain tissue architecture
from millimeter regional to nanometer synaptic scales in diverse chemically fixed
brain preparations, including rodent and human. CATS uses fixation-compatible
extracellular labeling and optical imaging, including stimulated emission depletion
or expansion microscopy, to comprehensively delineate cellular structures. It
enables three-dimensional reconstruction of single synapses and mapping of synaptic
connectivity by identification and analysis of putative synaptic cleft regions.
Applying CATS to the mouse hippocampal mossy fiber circuitry, we reconstructed
and quantified the synaptic input and output structure of identified neurons.
We furthermore demonstrate applicability to clinically derived human tissue samples,
including formalin-fixed paraffin-embedded routine diagnostic specimens, for visualizing
the cellular architecture of brain tissue in health and disease.
acknowledged_ssus:
- _id: ScienComp
- _id: Bio
- _id: PreCl
- _id: LifeSc
- _id: M-Shop
- _id: E-Lib
acknowledgement: 'We thank J. Vorlaufer, N. Agudelo-Dueñas, W. Jahr and A. Wartak
for microscope maintenance and troubleshooting; C. Kreuzinger, A. Freeman and I.
Erber for technical assistance; and M. Tomschik for support with obtaining human
samples. We gratefully acknowledge E. Miguel for setting up webKnossos and M. Šuplata
for computational support and hardware control. We are grateful to R. Shigemoto
and B. Bickel for generous support and M. Sixt and S. Boyd (Stanford University)
for discussions and critical reading of the paper. PSD95-HaloTag mice were kindly
provided by S. Grant (University of Edinburgh). We acknowledge expert support by
Institute of Science and Technology Austria’s scientific computing, imaging and
optics, preclinical and lab support facilities and by the Miba machine shop and
library. We gratefully acknowledge funding by the following sources: Austrian Science
Fund (FWF) grant I3600-B27 (J.G.D.); Austrian Science Fund (FWF) grant DK W1232
(J.G.D. and J.M.M.); Austrian Science Fund (FWF) grant Z 312-B27, Wittgenstein award
(P.J.); Austrian Science Fund (FWF) projects I4685-B, I6565-B (SYNABS) and DOC 33-B27
(R.H.); Gesellschaft für Forschungsförderung NÖ (NFB) grant LSC18-022 (J.G.D.);
European Union’s Horizon 2020 research and innovation programme, European Research
Council (ERC) grant 715508 – REVERSEAUTISM (G.N.); European Union’s Horizon 2020
research and innovation programme, European Research Council (ERC) grant 692692
– GIANTSYN (P.J.); Marie Skłodowska-Curie Actions Fellowship GA no. 665385 under
the EU Horizon 2020 program (J.M.M. and J.L.); and Marie Skłodowska-Curie Actions
Individual Fellowship no. 101026635 under the EU Horizon 2020 program (J.F.W.).'
article_processing_charge: Yes (in subscription journal)
article_type: original
author:
- first_name: Julia M
full_name: Michalska, Julia M
id: 443DB6DE-F248-11E8-B48F-1D18A9856A87
last_name: Michalska
orcid: 0000-0003-3862-1235
- first_name: Julia
full_name: Lyudchik, Julia
id: 46E28B80-F248-11E8-B48F-1D18A9856A87
last_name: Lyudchik
- first_name: Philipp
full_name: Velicky, Philipp
id: 39BDC62C-F248-11E8-B48F-1D18A9856A87
last_name: Velicky
orcid: 0000-0002-2340-7431
- first_name: Hana
full_name: Korinkova, Hana
id: ee3cb6ca-ec98-11ea-ae11-ff703e2254ed
last_name: Korinkova
- first_name: Jake
full_name: Watson, Jake
id: 63836096-4690-11EA-BD4E-32803DDC885E
last_name: Watson
orcid: 0000-0002-8698-3823
- first_name: Alban
full_name: Cenameri, Alban
id: 9ac8f577-2357-11eb-997a-e566c5550886
last_name: Cenameri
- first_name: Christoph M
full_name: Sommer, Christoph M
id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
last_name: Sommer
orcid: 0000-0003-1216-9105
- first_name: Nicole
full_name: Amberg, Nicole
id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87
last_name: Amberg
orcid: 0000-0002-3183-8207
- first_name: Alessandro
full_name: Venturino, Alessandro
id: 41CB84B2-F248-11E8-B48F-1D18A9856A87
last_name: Venturino
orcid: 0000-0003-2356-9403
- first_name: Karl
full_name: Roessler, Karl
last_name: Roessler
- first_name: Thomas
full_name: Czech, Thomas
last_name: Czech
- first_name: Romana
full_name: Höftberger, Romana
last_name: Höftberger
- first_name: Sandra
full_name: Siegert, Sandra
id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
last_name: Siegert
orcid: 0000-0001-8635-0877
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
- first_name: Peter M
full_name: Jonas, Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
- first_name: Johann G
full_name: Danzl, Johann G
id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
last_name: Danzl
orcid: 0000-0001-8559-3973
citation:
ama: Michalska JM, Lyudchik J, Velicky P, et al. Imaging brain tissue architecture
across millimeter to nanometer scales. Nature Biotechnology. 2024;42:1051-1064.
doi:10.1038/s41587-023-01911-8
apa: Michalska, J. M., Lyudchik, J., Velicky, P., Korinkova, H., Watson, J., Cenameri,
A., … Danzl, J. G. (2024). Imaging brain tissue architecture across millimeter
to nanometer scales. Nature Biotechnology. Springer Nature. https://doi.org/10.1038/s41587-023-01911-8
chicago: Michalska, Julia M, Julia Lyudchik, Philipp Velicky, Hana Korinkova, Jake
Watson, Alban Cenameri, Christoph M Sommer, et al. “Imaging Brain Tissue Architecture
across Millimeter to Nanometer Scales.” Nature Biotechnology. Springer
Nature, 2024. https://doi.org/10.1038/s41587-023-01911-8.
ieee: J. M. Michalska et al., “Imaging brain tissue architecture across millimeter
to nanometer scales,” Nature Biotechnology, vol. 42. Springer Nature, pp.
1051–1064, 2024.
ista: Michalska JM, Lyudchik J, Velicky P, Korinkova H, Watson J, Cenameri A, Sommer
CM, Amberg N, Venturino A, Roessler K, Czech T, Höftberger R, Siegert S, Novarino
G, Jonas PM, Danzl JG. 2024. Imaging brain tissue architecture across millimeter
to nanometer scales. Nature Biotechnology. 42, 1051–1064.
mla: Michalska, Julia M., et al. “Imaging Brain Tissue Architecture across Millimeter
to Nanometer Scales.” Nature Biotechnology, vol. 42, Springer Nature, 2024,
pp. 1051–64, doi:10.1038/s41587-023-01911-8.
short: J.M. Michalska, J. Lyudchik, P. Velicky, H. Korinkova, J. Watson, A. Cenameri,
C.M. Sommer, N. Amberg, A. Venturino, K. Roessler, T. Czech, R. Höftberger, S.
Siegert, G. Novarino, P.M. Jonas, J.G. Danzl, Nature Biotechnology 42 (2024) 1051–1064.
corr_author: '1'
date_created: 2023-09-03T22:01:15Z
date_published: 2024-07-01T00:00:00Z
date_updated: 2026-04-14T08:34:35Z
day: '01'
ddc:
- '570'
department:
- _id: SaSi
- _id: GaNo
- _id: PeJo
- _id: JoDa
- _id: Bio
- _id: RySh
doi: 10.1038/s41587-023-01911-8
ec_funded: 1
external_id:
isi:
- '001065254200001'
pmid:
- '37653226'
file:
- access_level: open_access
checksum: 57d5fafb16f02dcb9f7dddb1bd7e2a71
content_type: application/pdf
creator: dernst
date_created: 2025-01-09T07:48:01Z
date_updated: 2025-01-09T07:48:01Z
file_id: '18784'
file_name: 2024_NatureBiotech_Michalska.pdf
file_size: 26065165
relation: main_file
success: 1
file_date_updated: 2025-01-09T07:48:01Z
has_accepted_license: '1'
intvolume: ' 42'
isi: 1
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
page: 1051-1064
pmid: 1
project:
- _id: 265CB4D0-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: I03600
name: Optical control of synaptic function via adhesion molecules
- _id: 2548AE96-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: W1232
name: Molecular Drug Targets
- _id: 25C5A090-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: Z00312
name: Synaptic communication in neuronal microcircuits
- _id: 23889792-32DE-11EA-91FC-C7463DDC885E
grant_number: LS18-022
name: High content imaging to decode human immune cell interactions in health and
allergic disease
- _id: 25444568-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '715508'
name: Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo
and in vitro Models
- _id: 25B7EB9E-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '692692'
name: Biophysics and circuit function of a giant cortical glutamatergic synapse
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '665385'
name: International IST Doctoral Program
- _id: fc2be41b-9c52-11eb-aca3-faa90aa144e9
call_identifier: H2020
grant_number: '101026635'
name: Synaptic computations of the hippocampal CA3 circuitry
publication: Nature Biotechnology
publication_identifier:
eissn:
- 1546-1696
issn:
- 1087-0156
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
link:
- relation: software
url: https://github.com/danzllab/CATS
record:
- id: '18660'
relation: dissertation_contains
status: deleted
- id: '13126'
relation: research_data
status: public
- id: '18674'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: Imaging brain tissue architecture across millimeter to nanometer scales
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 42
year: '2024'
...
---
OA_place: publisher
_id: '15352'
abstract:
- lang: eng
text: "Epilepsy affects about 50 to 65 million people globally. It summarizes a
spectrum of neurological\r\ndisorders that have in common a hyperactivity of the
neuronal network resulting in seizures. A common\r\nassumption is that an imbalance
between neuronal excitation and inhibition is a key mechanism in\r\nseizure generation
and epileptogeneisis. In at least one-third of the patients, current therapies
have\r\nproven unsuccessful in treating seizure progression. One potential reason
could be that the therapies\r\nonly focus on neurons. Recent studies suggest that
neuronal hyperactivity causes a microglial\r\nresponse, which reinstates brain
homeostasis. Additionally, interactions between microglia and neurons\r\nhave
been shown to inhibit neuronal firing and dampen seizure activity. However, the
exact relationship\r\nbetween microglia and seizure progression in epilepsy is
yet to be elucidated. A main bottleneck is that\r\nseveral studies investigate
microglia dynamics in ex vivo slice models, which can severely affect the\r\nmicroglia
dynamics due to their rapid response to environmental changes. On the other hand,
in vivo\r\nstudies focus mostly on behavior characterization of the epileptic
seizure phenotype and their long-term\r\nconsequences on microglia activity leaving
out the direct consequences of acute seizure activity on\r\nmicroglia dynamics.\r\nHere,
we perform a pilot study to combine electroencephalography (EEG) and in vivo live
imaging to\r\ndirectly monitor and correlate the onset of seizure activity with
microglia response. To induce seizures,\r\nwe take advantage of the kainic acid
(KA) model, which represents similar neuropathological and\r\nelectroencephalographic
features seen in human patients with temporal lobe epilepsy (TLE). After\r\nconfirmation
of induction of the seizure and microglia activity in the hippocampus as a focal
point, we\r\ninvestigated whether these changes also reached the primary visual
cortex (V1) as a secondary\r\ngeneralized seizure activity. Indeed, we found that
microglia changed their morphology at high doses\r\nof KA in the V1. Next, we
optimized each of the two methodological components: for the EEG recording,\r\nour
initial attempts under the microscope suffered from extensive electrical noise,
which overlaid the\r\nactual signal. Thus, we built a customized Faraday-cage
and confirmed that the signal-to-noise ratio\r\nwas sufficiently reduced to be
able to record brain oscillatory activity. For the in vivo live imaging of\r\nmicroglia,
we had to optimize the imaging parameters, so that we would be able to detect
microglial\r\nprocesses in a sufficient resolution to track their process changes.
Finally, we combined both\r\nmethodologies with the KA model. We confirmed that
KA induced seizure activity and found first\r\nindication that those correlate
with microglia volume changes.\r\nOverall, we have developed a first methodological
approach, which allows the analysis of the acute\r\neffects of seizure onset on
microglia. Future studies will have to continue to optimize the drift during\r\nimaging
recording and the post-image analysis. "
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: PreCl
alternative_title:
- ISTA Master's Thesis
article_processing_charge: No
author:
- first_name: Julie Stefanie
full_name: Murmann, Julie Stefanie
id: 1d390868-f128-11eb-9611-a0ca5f7833b5
last_name: Murmann
citation:
ama: 'Murmann JS. Investigating acute microglia response to seizure activity in
vivo: Combining 2-Photon imaging and EEG recording. 2024. doi:10.15479/at:ista:15352'
apa: 'Murmann, J. S. (2024). Investigating acute microglia response to seizure
activity in vivo: Combining 2-Photon imaging and EEG recording. Institute
of Science and Technology Austria. https://doi.org/10.15479/at:ista:15352'
chicago: 'Murmann, Julie Stefanie. “Investigating Acute Microglia Response to Seizure
Activity in Vivo: Combining 2-Photon Imaging and EEG Recording.” Institute of
Science and Technology Austria, 2024. https://doi.org/10.15479/at:ista:15352.'
ieee: 'J. S. Murmann, “Investigating acute microglia response to seizure activity
in vivo: Combining 2-Photon imaging and EEG recording,” Institute of Science and
Technology Austria, 2024.'
ista: 'Murmann JS. 2024. Investigating acute microglia response to seizure activity
in vivo: Combining 2-Photon imaging and EEG recording. Institute of Science and
Technology Austria.'
mla: 'Murmann, Julie Stefanie. Investigating Acute Microglia Response to Seizure
Activity in Vivo: Combining 2-Photon Imaging and EEG Recording. Institute
of Science and Technology Austria, 2024, doi:10.15479/at:ista:15352.'
short: 'J.S. Murmann, Investigating Acute Microglia Response to Seizure Activity
in Vivo: Combining 2-Photon Imaging and EEG Recording, Institute of Science and
Technology Austria, 2024.'
corr_author: '1'
date_created: 2024-05-02T08:31:38Z
date_published: 2024-05-02T00:00:00Z
date_updated: 2026-04-07T13:05:00Z
day: '02'
ddc:
- '570'
degree_awarded: MS
department:
- _id: SaSi
- _id: GradSch
doi: 10.15479/at:ista:15352
file:
- access_level: open_access
checksum: 095817a6c944954ac3f277e547031a33
content_type: application/pdf
creator: cchlebak
date_created: 2024-05-02T12:26:13Z
date_updated: 2025-05-02T22:30:04Z
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language:
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month: '05'
oa: 1
oa_version: Published Version
page: '54'
publication_identifier:
issn:
- 2791-4585
publication_status: published
publisher: Institute of Science and Technology Austria
status: public
supervisor:
- first_name: Sandra
full_name: Siegert, Sandra
id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
last_name: Siegert
orcid: 0000-0001-8635-0877
title: 'Investigating acute microglia response to seizure activity in vivo: Combining
2-Photon imaging and EEG recording'
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2024'
...
---
_id: '13126'
abstract:
- lang: eng
text: Mapping the complex and dense arrangement of cells and their connectivity
in brain tissue demands nanoscale spatial resolution imaging. Super-resolution
optical microscopy excels at visualizing specific molecules and individual cells
but fails to provide tissue context. Here, we developed Comprehensive Analysis
of Tissues across Scales (CATS), a technology to densely map brain tissue architecture
from millimeter regional to nanometer synaptic scales in diverse chemically fixed
brain preparations, including rodent and human. CATS uses fixation-compatible
extracellular labeling and optical imaging, including stimulated emission depletion
or expansion microscopy, to comprehensively delineate cellular structures. It
enables three-dimensional reconstruction of single synapses and mapping of synaptic
connectivity by identification and analysis of putative synaptic cleft regions.
Applying CATS to the mouse hippocampal mossy fiber circuitry, we reconstructed
and quantified the synaptic input and output structure of identified neurons.
We furthermore demonstrate applicability to clinically derived human tissue samples,
including formalin-fixed paraffin-embedded routine diagnostic specimens, for visualizing
the cellular architecture of brain tissue in health and disease.
acknowledged_ssus:
- _id: ScienComp
- _id: Bio
- _id: PreCl
- _id: LifeSc
- _id: M-Shop
- _id: E-Lib
acknowledgement: "We thank Jakob Vorlaufer, Nathalie Agudelo-Dueñas, Wiebke Jahr,
Andreas Wartak for microscope maintenance and troubleshooting, Caroline Kreuzinger,
Anna Freeman, and Irene Erber for technical assistance and Matthias Tomschik for
support with obtaining human samples. We gratefully acknowledge Eder Miguel for
setting up webKnossos and Marek Šuplata for computational support and hardware control.
We are grateful to Ryuichi Shigemoto and Bernd Bickel for generous support, and
Michael Sixt and Scott Boyd (Stanford University) for discussions and critical reading
of the manuscript. PSD95-HaloTag mice were kindly provided by Seth Grant (University
of Edinburgh). We acknowledge expert support by IST Austria’s scientific computing,
imaging and optics, preclinical, and lab support facilities, and by the Library
and Miba machine shop.\r\nWe gratefully acknowledge funding by the following sources:
\r\nAustrian Science Fund (FWF) grant I3600-B27 (JGD)\r\nAustrian Science Fund (FWF)
grant DK W1232 (JGD, JMM)\r\nAustrian Science Fund (FWF) grant Z 312-B27, Wittgenstein
award (PJ)\r\nAustrian Science Funds (FWF) projects I4685-B, I6565-B (SYNABS) and
DOC 33-B27 (RH)\r\nGesellschaft für Forschungsförderung NÖ (NFB) grant LSC18-022
(JGD)\r\nEuropean Union’s Horizon 2020 research and innovation programme, European
Research Council (ERC) grant 715508 – REVERSEAUTISM (GN)\r\nEuropean Union’s Horizon
2020 research and innovation programme, European Research Council (ERC) grant 692692
– GIANTSYN (PJ)\r\nMarie Skłodowska-Curie Actions Fellowship GA no. 665385 under
the EU Horizon 2020 program (JMM, JL)\r\nMarie Skłodowska-Curie Actions Individual
Fellowship 101026635 under the EU Horizon 2020 program (JFW)"
article_processing_charge: No
author:
- first_name: Johann G
full_name: Danzl, Johann G
id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
last_name: Danzl
orcid: 0000-0001-8559-3973
citation:
ama: Danzl JG. Research data for the publication “Imaging brain tissue architecture
across millimeter to nanometer scales.” 2023. doi:10.15479/AT:ISTA:13126
apa: Danzl, J. G. (2023). Research data for the publication “Imaging brain tissue
architecture across millimeter to nanometer scales.” Institute of Science and
Technology Austria. https://doi.org/10.15479/AT:ISTA:13126
chicago: Danzl, Johann G. “Research Data for the Publication ‘Imaging Brain Tissue
Architecture across Millimeter to Nanometer Scales.’” Institute of Science and
Technology Austria, 2023. https://doi.org/10.15479/AT:ISTA:13126.
ieee: J. G. Danzl, “Research data for the publication ‘Imaging brain tissue architecture
across millimeter to nanometer scales.’” Institute of Science and Technology Austria,
2023.
ista: Danzl JG. 2023. Research data for the publication ‘Imaging brain tissue architecture
across millimeter to nanometer scales’, Institute of Science and Technology Austria,
10.15479/AT:ISTA:13126.
mla: Danzl, Johann G. Research Data for the Publication “Imaging Brain Tissue
Architecture across Millimeter to Nanometer Scales.” Institute of Science
and Technology Austria, 2023, doi:10.15479/AT:ISTA:13126.
short: J.G. Danzl, (2023).
contributor:
- first_name: Julia M
id: 443DB6DE-F248-11E8-B48F-1D18A9856A87
last_name: Michalska
- first_name: Julia
id: 46E28B80-F248-11E8-B48F-1D18A9856A87
last_name: Lyudchik
- first_name: Philipp
id: 39BDC62C-F248-11E8-B48F-1D18A9856A87
last_name: Velicky
orcid: 0000-0002-2340-7431
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id: ee3cb6ca-ec98-11ea-ae11-ff703e2254ed
last_name: Stefanickova
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last_name: Watson
orcid: 0000-0002-8698-3823
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id: 9ac8f577-2357-11eb-997a-e566c5550886
last_name: Cenameri
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last_name: Sommer
orcid: 0000-0003-1216-9105
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last_name: Amberg
orcid: 0000-0002-3183-8207
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last_name: Venturino
orcid: 0000-0003-2356-9403
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last_name: Roessler
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last_name: Czech
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last_name: Höftberger
- first_name: Sandra
id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
last_name: Siegert
orcid: 0000-0001-8635-0877
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id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
- first_name: Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
corr_author: '1'
date_created: 2023-06-07T07:15:12Z
date_published: 2023-08-04T00:00:00Z
date_updated: 2026-04-14T08:34:35Z
day: '04'
ddc:
- '610'
department:
- _id: JoDa
- _id: SaSi
- _id: GaNo
- _id: PeJo
- _id: Bio
- _id: RySh
doi: 10.15479/AT:ISTA:13126
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has_accepted_license: '1'
license: https://creativecommons.org/licenses/by-nc-sa/4.0/
month: '08'
oa: 1
oa_version: Published Version
project:
- _id: 265CB4D0-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: I03600
name: Optical control of synaptic function via adhesion molecules
- _id: 26AA4EF2-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: W1232-B24
name: Molecular Drug Targets
- _id: 25C5A090-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: Z00312
name: Synaptic communication in neuronal microcircuits
- _id: 23889792-32DE-11EA-91FC-C7463DDC885E
grant_number: LS18-022
name: High content imaging to decode human immune cell interactions in health and
allergic disease
- _id: 25444568-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '715508'
name: Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo
and in vitro Models
- _id: 25B7EB9E-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '692692'
name: Biophysics and circuit function of a giant cortical glutamatergic synapse
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '665385'
name: International IST Doctoral Program
- _id: fc2be41b-9c52-11eb-aca3-faa90aa144e9
call_identifier: H2020
grant_number: '101026635'
name: Synaptic computations of the hippocampal CA3 circuitry
publisher: Institute of Science and Technology Austria
related_material:
link:
- description: 'Original data for Fig. 5d, Fig. 5d (N2V) and Fig. 5f-i, provided
via an external link due to the large size (>10GB) of the datasets. '
relation: research_data
url: https://pub.ista.ac.at/group_danzl/data/CATS/
record:
- id: '14257'
relation: used_in_publication
status: public
status: public
title: Research data for the publication "Imaging brain tissue architecture across
millimeter to nanometer scales"
tmp:
image: /images/cc_by_nc_sa.png
legal_code_url: https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC
BY-NC-SA 4.0)
short: CC BY-NC-SA (4.0)
type: research_data
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2023'
...
---
_id: '14363'
abstract:
- lang: eng
text: Mitochondrial networks remodel their connectivity, content, and subcellular
localization to support optimized energy production in conditions of increased
environmental or cellular stress. Microglia rely on mitochondria to respond to
these stressors, however our knowledge about mitochondrial networks and their
adaptations in microglia in vivo is limited. Here, we generate a mouse model that
selectively labels mitochondria in microglia. We identify that mitochondrial networks
are more fragmented with increased content and perinuclear localization in vitro
vs. in vivo. Mitochondrial networks adapt similarly in microglia closest to the
injury site after optic nerve crush. Preventing microglial UCP2 increase after
injury by selective knockout induces cellular stress. This results in mitochondrial
hyperfusion in male microglia, a phenotype absent in females due to circulating
estrogens. Our results establish the foundation for mitochondrial network analysis
of microglia in vivo, emphasizing the importance of mitochondrial-based sex effects
of microglia in other pathologies.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: PreCl
acknowledgement: We thank the Scientific Service Units (SSU) of ISTA through resources
provided by the Imaging and Optics Facility (IOF), the Lab Support Facility (LSF),
and the Pre-Clinical Facility (PCF) team, specifically Sonja Haslinger and Michael
Schunn for excellent mouse colony management and support. This research was supported
by the FWF Sonderforschungsbereich F83 (to E.E.P). We thank Bálint Nagy, Ryan John
A. Cubero, Marco Benevento and all members of the Siegert group for constant feedback
on the project and article.
article_number: '107780'
article_processing_charge: Yes
article_type: original
author:
- first_name: Margaret E
full_name: Maes, Margaret E
id: 3838F452-F248-11E8-B48F-1D18A9856A87
last_name: Maes
orcid: 0000-0001-9642-1085
- first_name: Gloria
full_name: Colombo, Gloria
id: 3483CF6C-F248-11E8-B48F-1D18A9856A87
last_name: Colombo
orcid: 0000-0001-9434-8902
- first_name: Florianne E
full_name: Schoot Uiterkamp, Florianne E
id: 3526230C-F248-11E8-B48F-1D18A9856A87
last_name: Schoot Uiterkamp
- first_name: Felix
full_name: Sternberg, Felix
last_name: Sternberg
- first_name: Alessandro
full_name: Venturino, Alessandro
id: 41CB84B2-F248-11E8-B48F-1D18A9856A87
last_name: Venturino
orcid: 0000-0003-2356-9403
- first_name: Elena E.
full_name: Pohl, Elena E.
last_name: Pohl
- first_name: Sandra
full_name: Siegert, Sandra
id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
last_name: Siegert
orcid: 0000-0001-8635-0877
citation:
ama: Maes ME, Colombo G, Schoot Uiterkamp FE, et al. Mitochondrial network adaptations
of microglia reveal sex-specific stress response after injury and UCP2 knockout.
iScience. 2023;26(10). doi:10.1016/j.isci.2023.107780
apa: Maes, M. E., Colombo, G., Schoot Uiterkamp, F. E., Sternberg, F., Venturino,
A., Pohl, E. E., & Siegert, S. (2023). Mitochondrial network adaptations of
microglia reveal sex-specific stress response after injury and UCP2 knockout.
IScience. Elsevier. https://doi.org/10.1016/j.isci.2023.107780
chicago: Maes, Margaret E, Gloria Colombo, Florianne E Schoot Uiterkamp, Felix Sternberg,
Alessandro Venturino, Elena E. Pohl, and Sandra Siegert. “Mitochondrial Network
Adaptations of Microglia Reveal Sex-Specific Stress Response after Injury and
UCP2 Knockout.” IScience. Elsevier, 2023. https://doi.org/10.1016/j.isci.2023.107780.
ieee: M. E. Maes et al., “Mitochondrial network adaptations of microglia
reveal sex-specific stress response after injury and UCP2 knockout,” iScience,
vol. 26, no. 10. Elsevier, 2023.
ista: Maes ME, Colombo G, Schoot Uiterkamp FE, Sternberg F, Venturino A, Pohl EE,
Siegert S. 2023. Mitochondrial network adaptations of microglia reveal sex-specific
stress response after injury and UCP2 knockout. iScience. 26(10), 107780.
mla: Maes, Margaret E., et al. “Mitochondrial Network Adaptations of Microglia Reveal
Sex-Specific Stress Response after Injury and UCP2 Knockout.” IScience,
vol. 26, no. 10, 107780, Elsevier, 2023, doi:10.1016/j.isci.2023.107780.
short: M.E. Maes, G. Colombo, F.E. Schoot Uiterkamp, F. Sternberg, A. Venturino,
E.E. Pohl, S. Siegert, IScience 26 (2023).
corr_author: '1'
date_created: 2023-09-24T22:01:11Z
date_published: 2023-10-20T00:00:00Z
date_updated: 2024-10-09T21:07:01Z
day: '20'
ddc:
- '570'
department:
- _id: SaSi
doi: 10.1016/j.isci.2023.107780
external_id:
isi:
- '001080403500001'
pmid:
- '37731609'
file:
- access_level: open_access
checksum: be1a560efdd96d20712311f4fc54aac2
content_type: application/pdf
creator: dernst
date_created: 2023-11-07T08:53:21Z
date_updated: 2023-11-07T08:53:21Z
file_id: '14497'
file_name: 2023_iScience_Maes.pdf
file_size: 8197935
relation: main_file
success: 1
file_date_updated: 2023-11-07T08:53:21Z
has_accepted_license: '1'
intvolume: ' 26'
isi: 1
issue: '10'
language:
- iso: eng
month: '10'
oa: 1
oa_version: Published Version
pmid: 1
publication: iScience
publication_identifier:
eissn:
- 2589-0042
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: Mitochondrial network adaptations of microglia reveal sex-specific stress response
after injury and UCP2 knockout
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 26
year: '2023'
...
---
_id: '14401'
abstract:
- lang: eng
text: "Background: \r\nPro-apoptotic BAX is a central mediator of retinal ganglion
cell (RGC) death after optic nerve damage. BAX activation occurs in two stages
including translocation of latent BAX to the mitochondrial outer membrane (MOM)
and then permeabilization of the MOM to facilitate the release of apoptotic signaling
molecules. As a critical component of RGC death, BAX is an attractive target for
neuroprotective therapies and an understanding of the kinetics of BAX activation
and the mechanisms controlling the two stages of this process in RGCs is potentially
valuable in informing the development of a neuroprotective strategy.\r\nMethods:\r\nThe
kinetics of BAX translocation were assessed by both static and live-cell imaging
of a GFP-BAX fusion protein introduced into RGCs using AAV2-mediated gene transfer
in mice. Activation of BAX was achieved using an acute optic nerve crush (ONC)
protocol. Live-cell imaging of GFP-BAX was achieved using explants of mouse retina
harvested 7 days after ONC. Kinetics of translocation in RGCs were compared to
GFP-BAX translocation in 661W tissue culture cells. Permeabilization of GFP-BAX
was assessed by staining with the 6A7 monoclonal antibody, which recognizes a
conformational change in this protein after MOM insertion. Assessment of individual
kinases associated with both stages of activation was made using small molecule
inhibitors injected into the vitreous either independently or in concert with
ONC surgery. The contribution of the Dual Leucine Zipper-JUN-N-Terminal Kinase
cascade was evaluated using mice with a double conditional knock-out of both Mkk4
and Mkk7.\r\nResults:\r\nONC induces the translocation of GFP-BAX in RGCs at a
slower rate and with less intracellular synchronicity than 661W cells, but exhibits
less variability among mitochondrial foci within a single cell. GFP-BAX was also
found to translocate in all compartments of an RGC including the dendritic arbor
and axon. Approximately 6% of translocating RGCs exhibited retrotranslocation
of BAX immediately following translocation. Unlike tissue culture cells, which
exhibit simultaneous translocation and permeabilization, RGCs exhibited a significant
delay between these two stages, similar to detached cells undergoing anoikis.
Translocation, with minimal permeabilization could be induced in a subset of RGCs
using an inhibitor of Focal Adhesion Kinase (PF573228). Permeabilization after
ONC, in a majority of RGCs, could be inhibited with a broad spectrum kinase inhibitor
(sunitinib) or a selective inhibitor for p38/MAPK14 (SB203580). Intervention of
DLK-JNK axis signaling abrogated GFP-BAX translocation after ONC.\r\nConclusions:\r\nA
comparison between BAX activation kinetics in tissue culture cells and in cells
of a complex tissue environment shows distinct differences indicating that caution
should be used when translating findings from one condition to the other. RGCs
exhibit both a delay between translocation and permeabilization and the ability
for translocated BAX to be retrotranslocated, suggesting several stages at which
intervention of the activation process could be exploited in the design of a therapeutic
strategy."
acknowledgement: "The authors would like to thank Mr. Joel Dietz for management of
the mouse colony and helpful advice for conducting quantitative PCR studies and
Mr. Santoshi Kinoshita at the Translational Research Initiative in Pathology laboratory
at the University of Wisconsin-Madison for cutting sections analyzed in this study.\r\nThis
work was supported by National Eye Institute grants R01 EY030123 (RWN), R01 EY018606
(RTL), P30 EY016665 (Department of Ophthalmology and Visual Sciences, University
of Wisconsin-Madison), T32 EY027721 (RJD) and F31 EY030739 (OJM). Additional funding
was provided by the BrightFocus Foundation (RWN) and unrestricted grants from Research
to Prevent Blindness, Inc to the Department of Ophthalmology and Visual Sciences
(University of Wisconsin-Madison) and to the Department of Ophthalmology (University
of Rochester)."
article_number: '67'
article_processing_charge: Yes
article_type: original
author:
- first_name: Margaret E
full_name: Maes, Margaret E
id: 3838F452-F248-11E8-B48F-1D18A9856A87
last_name: Maes
orcid: 0000-0001-9642-1085
- first_name: Ryan J.
full_name: Donahue, Ryan J.
last_name: Donahue
- first_name: Cassandra L.
full_name: Schlamp, Cassandra L.
last_name: Schlamp
- first_name: Olivia J.
full_name: Marola, Olivia J.
last_name: Marola
- first_name: Richard T.
full_name: Libby, Richard T.
last_name: Libby
- first_name: Robert W.
full_name: Nickells, Robert W.
last_name: Nickells
citation:
ama: Maes ME, Donahue RJ, Schlamp CL, Marola OJ, Libby RT, Nickells RW. BAX activation
in mouse retinal ganglion cells occurs in two temporally and mechanistically distinct
steps. Molecular Neurodegeneration. 2023;18. doi:10.1186/s13024-023-00659-8
apa: Maes, M. E., Donahue, R. J., Schlamp, C. L., Marola, O. J., Libby, R. T., &
Nickells, R. W. (2023). BAX activation in mouse retinal ganglion cells occurs
in two temporally and mechanistically distinct steps. Molecular Neurodegeneration.
Springer Nature. https://doi.org/10.1186/s13024-023-00659-8
chicago: Maes, Margaret E, Ryan J. Donahue, Cassandra L. Schlamp, Olivia J. Marola,
Richard T. Libby, and Robert W. Nickells. “BAX Activation in Mouse Retinal Ganglion
Cells Occurs in Two Temporally and Mechanistically Distinct Steps.” Molecular
Neurodegeneration. Springer Nature, 2023. https://doi.org/10.1186/s13024-023-00659-8.
ieee: M. E. Maes, R. J. Donahue, C. L. Schlamp, O. J. Marola, R. T. Libby, and R.
W. Nickells, “BAX activation in mouse retinal ganglion cells occurs in two temporally
and mechanistically distinct steps,” Molecular Neurodegeneration, vol.
18. Springer Nature, 2023.
ista: Maes ME, Donahue RJ, Schlamp CL, Marola OJ, Libby RT, Nickells RW. 2023. BAX
activation in mouse retinal ganglion cells occurs in two temporally and mechanistically
distinct steps. Molecular Neurodegeneration. 18, 67.
mla: Maes, Margaret E., et al. “BAX Activation in Mouse Retinal Ganglion Cells Occurs
in Two Temporally and Mechanistically Distinct Steps.” Molecular Neurodegeneration,
vol. 18, 67, Springer Nature, 2023, doi:10.1186/s13024-023-00659-8.
short: M.E. Maes, R.J. Donahue, C.L. Schlamp, O.J. Marola, R.T. Libby, R.W. Nickells,
Molecular Neurodegeneration 18 (2023).
date_created: 2023-10-08T22:01:15Z
date_published: 2023-09-26T00:00:00Z
date_updated: 2025-04-23T13:09:05Z
day: '26'
ddc:
- '570'
department:
- _id: SaSi
doi: 10.1186/s13024-023-00659-8
external_id:
isi:
- '001071403800001'
pmid:
- '37752598'
file:
- access_level: open_access
checksum: 3aa218ddea4a082d8fd5e196ae55ca06
content_type: application/pdf
creator: dernst
date_created: 2024-01-30T14:33:31Z
date_updated: 2024-01-30T14:33:31Z
file_id: '14917'
file_name: 2023_MolecularNeurodegeneration_Maes.pdf
file_size: 11568350
relation: main_file
success: 1
file_date_updated: 2024-01-30T14:33:31Z
has_accepted_license: '1'
intvolume: ' 18'
isi: 1
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
pmid: 1
publication: Molecular Neurodegeneration
publication_identifier:
eissn:
- 1750-1326
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: BAX activation in mouse retinal ganglion cells occurs in two temporally and
mechanistically distinct steps
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 18
year: '2023'
...
---
_id: '11478'
abstract:
- lang: eng
text: Cerebral organoids differentiated from human-induced pluripotent stem cells
(hiPSC) provide a unique opportunity to investigate brain development. However,
organoids usually lack microglia, brain-resident immune cells, which are present
in the early embryonic brain and participate in neuronal circuit development.
Here, we find IBA1+ microglia-like cells alongside retinal cups between week 3
and 4 in 2.5D culture with an unguided retinal organoid differentiation protocol.
Microglia do not infiltrate the neuroectoderm and instead enrich within non-pigmented,
3D-cystic compartments that develop in parallel to the 3D-retinal organoids. When
we guide the retinal organoid differentiation with low-dosed BMP4, we prevent
cup development and enhance microglia and 3D-cysts formation. Mass spectrometry
identifies these 3D-cysts to express mesenchymal and epithelial markers. We confirmed
this microglia-preferred environment also within the unguided protocol, providing
insight into microglial behavior and migration and offer a model to study how
they enter and distribute within the human brain.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
acknowledgement: We thank the scientific service units at ISTA, specifically the lab
support facility and imaging & optics facility for their support; Nicolas Armel
for performing the Mass Spectrometry. We thank Alexandra Lang and Tanja Peilnsteiner
for their help in human brain tissue collection, Rouven Schulz for his insights
into the functional assays We thank all members of the Siegert group for constant
feedback on the project and Margaret Maes, Rouven Schulz, and Marco Benevento for
feedback on the manuscript. This project has received funding from the European
Research Council (ERC) under the European Union’s Horizon 2020 research and innovation
program (grant No. 715571 to S.S.) and from the Gesellschaft für Forschungsförderung
Niederösterreich (grant No. Sc19-017 to V.H.).
article_number: '104580'
article_processing_charge: Yes
article_type: original
author:
- first_name: Katarina
full_name: Bartalska, Katarina
id: 4D883232-F248-11E8-B48F-1D18A9856A87
last_name: Bartalska
- first_name: Verena
full_name: Hübschmann, Verena
id: 32B7C918-F248-11E8-B48F-1D18A9856A87
last_name: Hübschmann
- first_name: Medina
full_name: Korkut, Medina
id: 4B51CE74-F248-11E8-B48F-1D18A9856A87
last_name: Korkut
orcid: 0000-0003-4309-2251
- first_name: Ryan J
full_name: Cubero, Ryan J
id: 850B2E12-9CD4-11E9-837F-E719E6697425
last_name: Cubero
orcid: 0000-0003-0002-1867
- first_name: Alessandro
full_name: Venturino, Alessandro
id: 41CB84B2-F248-11E8-B48F-1D18A9856A87
last_name: Venturino
orcid: 0000-0003-2356-9403
- first_name: Karl
full_name: Rössler, Karl
last_name: Rössler
- first_name: Thomas
full_name: Czech, Thomas
last_name: Czech
- first_name: Sandra
full_name: Siegert, Sandra
id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
last_name: Siegert
orcid: 0000-0001-8635-0877
citation:
ama: Bartalska K, Hübschmann V, Korkut M, et al. A systematic characterization of
microglia-like cell occurrence during retinal organoid differentiation. iScience.
2022;25(7). doi:10.1016/j.isci.2022.104580
apa: Bartalska, K., Hübschmann, V., Korkut, M., Cubero, R. J., Venturino, A., Rössler,
K., … Siegert, S. (2022). A systematic characterization of microglia-like cell
occurrence during retinal organoid differentiation. IScience. Elsevier.
https://doi.org/10.1016/j.isci.2022.104580
chicago: Bartalska, Katarina, Verena Hübschmann, Medina Korkut, Ryan J Cubero, Alessandro
Venturino, Karl Rössler, Thomas Czech, and Sandra Siegert. “A Systematic Characterization
of Microglia-like Cell Occurrence during Retinal Organoid Differentiation.” IScience.
Elsevier, 2022. https://doi.org/10.1016/j.isci.2022.104580.
ieee: K. Bartalska et al., “A systematic characterization of microglia-like
cell occurrence during retinal organoid differentiation,” iScience, vol.
25, no. 7. Elsevier, 2022.
ista: Bartalska K, Hübschmann V, Korkut M, Cubero RJ, Venturino A, Rössler K, Czech
T, Siegert S. 2022. A systematic characterization of microglia-like cell occurrence
during retinal organoid differentiation. iScience. 25(7), 104580.
mla: Bartalska, Katarina, et al. “A Systematic Characterization of Microglia-like
Cell Occurrence during Retinal Organoid Differentiation.” IScience, vol.
25, no. 7, 104580, Elsevier, 2022, doi:10.1016/j.isci.2022.104580.
short: K. Bartalska, V. Hübschmann, M. Korkut, R.J. Cubero, A. Venturino, K. Rössler,
T. Czech, S. Siegert, IScience 25 (2022).
corr_author: '1'
date_created: 2022-07-03T22:01:33Z
date_published: 2022-07-15T00:00:00Z
date_updated: 2026-04-07T11:51:43Z
day: '15'
ddc:
- '610'
department:
- _id: SaSi
doi: 10.1016/j.isci.2022.104580
ec_funded: 1
external_id:
isi:
- '000830428500005'
pmid:
- '35789843'
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file_name: 2022_iScience_Bartalska.pdf
file_size: 19400048
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file_date_updated: 2022-07-04T08:19:25Z
has_accepted_license: '1'
intvolume: ' 25'
isi: 1
issue: '7'
language:
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month: '07'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 25D4A630-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '715571'
name: Microglia action towards neuronal circuit formation and function in health
and disease
- _id: B67AFEDC-15C9-11EA-A837-991A96BB2854
name: IST Austria Open Access Fund
- _id: 9B99D380-BA93-11EA-9121-9846C619BF3A
grant_number: SC19-017
name: How human microglia shape developing neurons during health and inflammation
publication: iScience
publication_identifier:
eissn:
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publication_status: published
publisher: Elsevier
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status: public
title: A systematic characterization of microglia-like cell occurrence during retinal
organoid differentiation
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
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author:
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full_name: Schulz, Rouven
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last_name: Schulz
orcid: 0000-0001-5297-733X
citation:
ama: Schulz R. Source Data (Chimeric GPCRs mimic distinct signaling pathways and
modulate microglia responses). 2022. doi:10.15479/AT:ISTA:11542
apa: Schulz, R. (2022). Source Data (Chimeric GPCRs mimic distinct signaling pathways
and modulate microglia responses). Institute of Science and Technology Austria.
https://doi.org/10.15479/AT:ISTA:11542
chicago: Schulz, Rouven. “Source Data (Chimeric GPCRs Mimic Distinct Signaling Pathways
and Modulate Microglia Responses).” Institute of Science and Technology Austria,
2022. https://doi.org/10.15479/AT:ISTA:11542.
ieee: R. Schulz, “Source Data (Chimeric GPCRs mimic distinct signaling pathways
and modulate microglia responses).” Institute of Science and Technology Austria,
2022.
ista: Schulz R. 2022. Source Data (Chimeric GPCRs mimic distinct signaling pathways
and modulate microglia responses), Institute of Science and Technology Austria,
10.15479/AT:ISTA:11542.
mla: Schulz, Rouven. Source Data (Chimeric GPCRs Mimic Distinct Signaling Pathways
and Modulate Microglia Responses). Institute of Science and Technology Austria,
2022, doi:10.15479/AT:ISTA:11542.
short: R. Schulz, (2022).
contributor:
- contributor_type: contact_person
first_name: Sandra
id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
last_name: Siegert
orcid: 0000-0001-8635-0877
corr_author: '1'
date_created: 2022-07-08T11:03:02Z
date_published: 2022-01-01T00:00:00Z
date_updated: 2025-04-15T07:27:21Z
department:
- _id: GradSch
- _id: SaSi
doi: 10.15479/AT:ISTA:11542
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publisher: Institute of Science and Technology Austria
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url: https://www.biorxiv.org/content/10.1101/2021.06.21.449162v1
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title: Source Data (Chimeric GPCRs mimic distinct signaling pathways and modulate
microglia responses)
tmp:
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legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
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type: research_data
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2022'
...
---
OA_place: publisher
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abstract:
- lang: eng
text: "G protein-coupled receptors (GPCRs) respond to specific ligands and regulate
multiple processes ranging from cell growth and immune responses to neuronal signal
transmission. However, ligands for many GPCRs remain unknown, suffer from off-target
effects or have poor bioavailability. Additional challenges exist to dissect cell-type
specific responses when the same GPCR is expressed on several cell types within
the body. Here, we overcome these limitations by engineering DREADD-based GPCR
chimeras that selectively bind their agonist clozapine-N-oxide (CNO) and mimic
a GPCR-of-interest in a desired cell type.\r\nWe validated our approach with β2-adrenergic
receptor (β2AR/ADRB2) and show that our chimeric DREADD-β2AR triggers comparable
responses on second messenger and kinase activity, post-translational modifications,
and protein-protein interactions. Since β2AR is also enriched in microglia, which
can drive inflammation in the central nervous system, we expressed chimeric DREADD-β2AR
in primary microglia and successfully recapitulate β2AR-mediated filopodia formation
through CNO stimulation. To dissect the role of selected GPCRs during microglial
inflammation, we additionally generated DREADD-based chimeras for microglia-enriched
GPR65 and GPR109A/HCAR2. In a microglia cell line, DREADD-β2AR and DREADD-GPR65
both modulated the inflammatory response with a similar profile as endogenously
expressed β2AR, while DREADD-GPR109A showed no impact.\r\nOur DREADD-based approach
provides the means to obtain mechanistic and functional insights into GPCR signaling
on a cell-type specific level."
acknowledged_ssus:
- _id: Bio
- _id: PreCl
- _id: LifeSc
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Rouven
full_name: Schulz, Rouven
id: 4C5E7B96-F248-11E8-B48F-1D18A9856A87
last_name: Schulz
orcid: 0000-0001-5297-733X
citation:
ama: Schulz R. Chimeric G protein-coupled receptors mimic distinct signaling pathways
and modulate microglia function. 2022. doi:10.15479/at:ista:11945
apa: Schulz, R. (2022). Chimeric G protein-coupled receptors mimic distinct signaling
pathways and modulate microglia function. Institute of Science and Technology
Austria. https://doi.org/10.15479/at:ista:11945
chicago: Schulz, Rouven. “Chimeric G Protein-Coupled Receptors Mimic Distinct Signaling
Pathways and Modulate Microglia Function.” Institute of Science and Technology
Austria, 2022. https://doi.org/10.15479/at:ista:11945.
ieee: R. Schulz, “Chimeric G protein-coupled receptors mimic distinct signaling
pathways and modulate microglia function,” Institute of Science and Technology
Austria, 2022.
ista: Schulz R. 2022. Chimeric G protein-coupled receptors mimic distinct signaling
pathways and modulate microglia function. Institute of Science and Technology
Austria.
mla: Schulz, Rouven. Chimeric G Protein-Coupled Receptors Mimic Distinct Signaling
Pathways and Modulate Microglia Function. Institute of Science and Technology
Austria, 2022, doi:10.15479/at:ista:11945.
short: R. Schulz, Chimeric G Protein-Coupled Receptors Mimic Distinct Signaling
Pathways and Modulate Microglia Function, Institute of Science and Technology
Austria, 2022.
corr_author: '1'
date_created: 2022-08-23T11:33:11Z
date_published: 2022-08-23T00:00:00Z
date_updated: 2026-04-07T14:17:59Z
day: '23'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: GradSch
- _id: SaSi
doi: 10.15479/at:ista:11945
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name: Modulating microglia through G protein-coupled receptor (GPCR) signaling
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
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relation: dissertation_contains
status: public
status: public
supervisor:
- first_name: Sandra
full_name: Siegert, Sandra
id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
last_name: Siegert
orcid: 0000-0001-8635-0877
title: Chimeric G protein-coupled receptors mimic distinct signaling pathways and
modulate microglia function
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2022'
...
---
_id: '11995'
abstract:
- lang: eng
text: G protein-coupled receptors (GPCRs) regulate processes ranging from immune
responses to neuronal signaling. However, ligands for many GPCRs remain unknown,
suffer from off-target effects or have poor bioavailability. Additionally, dissecting
cell type-specific responses is challenging when the same GPCR is expressed on
different cells within a tissue. Here, we overcome these limitations by engineering
DREADD-based GPCR chimeras that bind clozapine-N-oxide and mimic a GPCR-of-interest.
We show that chimeric DREADD-β2AR triggers responses comparable to β2AR on second
messenger and kinase activity, post-translational modifications, and protein-protein
interactions. Moreover, we successfully recapitulate β2AR-mediated filopodia formation
in microglia, an immune cell capable of driving central nervous system inflammation.
When dissecting microglial inflammation, we included two additional DREADD-based
chimeras mimicking microglia-enriched GPR65 and GPR109A. DREADD-β2AR and DREADD-GPR65
modulate the inflammatory response with high similarity to endogenous β2AR, while
DREADD-GPR109A shows no impact. Our DREADD-based approach allows investigation
of cell type-dependent pathways without known endogenous ligands.
acknowledged_ssus:
- _id: PreCl
- _id: Bio
- _id: LifeSc
acknowledgement: The authors thank the Scientific Service Units at ISTA, in particular
the Molecular Biology Service of the Lab Support Facility, Imaging & Optics Facility,
and the Preclinical Facility, and the Novarino group, Harald Janoviak, and Marco
Benevento for sharing reagents and expertise. This research was supported by a DOC
Fellowship (24979) awarded to R.S. by the Austrian Academy of Sciences.
article_number: '4728'
article_processing_charge: No
article_type: original
author:
- first_name: Rouven
full_name: Schulz, Rouven
id: 4C5E7B96-F248-11E8-B48F-1D18A9856A87
last_name: Schulz
orcid: 0000-0001-5297-733X
- first_name: Medina
full_name: Korkut, Medina
id: 4B51CE74-F248-11E8-B48F-1D18A9856A87
last_name: Korkut
orcid: 0000-0003-4309-2251
- first_name: Alessandro
full_name: Venturino, Alessandro
id: 41CB84B2-F248-11E8-B48F-1D18A9856A87
last_name: Venturino
orcid: 0000-0003-2356-9403
- first_name: Gloria
full_name: Colombo, Gloria
id: 3483CF6C-F248-11E8-B48F-1D18A9856A87
last_name: Colombo
orcid: 0000-0001-9434-8902
- first_name: Sandra
full_name: Siegert, Sandra
id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
last_name: Siegert
orcid: 0000-0001-8635-0877
citation:
ama: Schulz R, Korkut M, Venturino A, Colombo G, Siegert S. Chimeric GPCRs mimic
distinct signaling pathways and modulate microglia responses. Nature Communications.
2022;13. doi:10.1038/s41467-022-32390-1
apa: Schulz, R., Korkut, M., Venturino, A., Colombo, G., & Siegert, S. (2022).
Chimeric GPCRs mimic distinct signaling pathways and modulate microglia responses.
Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-022-32390-1
chicago: Schulz, Rouven, Medina Korkut, Alessandro Venturino, Gloria Colombo, and
Sandra Siegert. “Chimeric GPCRs Mimic Distinct Signaling Pathways and Modulate
Microglia Responses.” Nature Communications. Springer Nature, 2022. https://doi.org/10.1038/s41467-022-32390-1.
ieee: R. Schulz, M. Korkut, A. Venturino, G. Colombo, and S. Siegert, “Chimeric
GPCRs mimic distinct signaling pathways and modulate microglia responses,” Nature
Communications, vol. 13. Springer Nature, 2022.
ista: Schulz R, Korkut M, Venturino A, Colombo G, Siegert S. 2022. Chimeric GPCRs
mimic distinct signaling pathways and modulate microglia responses. Nature Communications.
13, 4728.
mla: Schulz, Rouven, et al. “Chimeric GPCRs Mimic Distinct Signaling Pathways and
Modulate Microglia Responses.” Nature Communications, vol. 13, 4728, Springer
Nature, 2022, doi:10.1038/s41467-022-32390-1.
short: R. Schulz, M. Korkut, A. Venturino, G. Colombo, S. Siegert, Nature Communications
13 (2022).
corr_author: '1'
date_created: 2022-08-28T22:01:59Z
date_published: 2022-08-15T00:00:00Z
date_updated: 2026-04-07T14:17:58Z
day: '15'
ddc:
- '570'
department:
- _id: SaSi
doi: 10.1038/s41467-022-32390-1
external_id:
isi:
- '000840984400032'
pmid:
- '35970889'
file:
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checksum: 191d9db0266e14a28d3a56dc7f65da84
content_type: application/pdf
creator: cchlebak
date_created: 2022-08-29T06:44:30Z
date_updated: 2022-08-29T06:44:30Z
file_id: '12002'
file_name: 2022_NatComm_Schulz.pdf
file_size: 7317396
relation: main_file
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file_date_updated: 2022-08-29T06:44:30Z
has_accepted_license: '1'
intvolume: ' 13'
isi: 1
language:
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month: '08'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 267F75D8-B435-11E9-9278-68D0E5697425
name: Modulating microglia through G protein-coupled receptor (GPCR) signaling
publication: Nature Communications
publication_identifier:
eissn:
- 2041-1723
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
link:
- description: News on ISTA website
relation: press_release
url: https://ista.ac.at/en/news/dreaddful-mimicry/
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relation: part_of_dissertation
status: public
scopus_import: '1'
status: public
title: Chimeric GPCRs mimic distinct signaling pathways and modulate microglia responses
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 13
year: '2022'
...
---
_id: '12117'
abstract:
- lang: eng
text: "To understand how potential gene manipulations affect in vitro microglia,
we provide a set of short protocols to evaluate microglia identity and function.
We detail steps for immunostaining to determine microglia identity. We describe
three functional assays for microglia: phagocytosis, calcium response following
ATP stimulation, and cytokine expression upon inflammatory stimuli. We apply these
protocols to human induced-pluripotent-stem-cell (hiPSC)-derived microglia, but
they can be also applied to other in vitro microglial models including primary
mouse microglia.\r\nFor complete details on the use and execution of this protocol,
please refer to Bartalska et al. (2022).1"
acknowledged_ssus:
- _id: Bio
acknowledgement: This project has received funding from the European Research Council
(ERC) under the European Union’s Horizon 2020 research and innovation program (grant
No. 715571 to S.S.) and from the Gesellschaft für Forschungsförderung Niederösterreich
(grant No. Sc19-017 to V.H.). We thank Rouven Schulz and Alessandro Venturino for
their insights into functional assays and data analysis, Verena Seiboth for insights
into necessary institutional permission, and ISTA imaging & optics facility (IOF)
especially Bernhard Hochreiter for their support.
article_number: '101866'
article_processing_charge: No
article_type: letter_note
author:
- first_name: Verena
full_name: Hübschmann, Verena
id: 32B7C918-F248-11E8-B48F-1D18A9856A87
last_name: Hübschmann
- first_name: Medina
full_name: Korkut, Medina
id: 4B51CE74-F248-11E8-B48F-1D18A9856A87
last_name: Korkut
orcid: 0000-0003-4309-2251
- first_name: Sandra
full_name: Siegert, Sandra
id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
last_name: Siegert
orcid: 0000-0001-8635-0877
citation:
ama: Hübschmann V, Korkut M, Siegert S. Assessing human iPSC-derived microglia identity
and function by immunostaining, phagocytosis, calcium activity, and inflammation
assay. STAR Protocols. 2022;3(4). doi:10.1016/j.xpro.2022.101866
apa: Hübschmann, V., Korkut, M., & Siegert, S. (2022). Assessing human iPSC-derived
microglia identity and function by immunostaining, phagocytosis, calcium activity,
and inflammation assay. STAR Protocols. Elsevier. https://doi.org/10.1016/j.xpro.2022.101866
chicago: Hübschmann, Verena, Medina Korkut, and Sandra Siegert. “Assessing Human
IPSC-Derived Microglia Identity and Function by Immunostaining, Phagocytosis,
Calcium Activity, and Inflammation Assay.” STAR Protocols. Elsevier, 2022.
https://doi.org/10.1016/j.xpro.2022.101866.
ieee: V. Hübschmann, M. Korkut, and S. Siegert, “Assessing human iPSC-derived microglia
identity and function by immunostaining, phagocytosis, calcium activity, and inflammation
assay,” STAR Protocols, vol. 3, no. 4. Elsevier, 2022.
ista: Hübschmann V, Korkut M, Siegert S. 2022. Assessing human iPSC-derived microglia
identity and function by immunostaining, phagocytosis, calcium activity, and inflammation
assay. STAR Protocols. 3(4), 101866.
mla: Hübschmann, Verena, et al. “Assessing Human IPSC-Derived Microglia Identity
and Function by Immunostaining, Phagocytosis, Calcium Activity, and Inflammation
Assay.” STAR Protocols, vol. 3, no. 4, 101866, Elsevier, 2022, doi:10.1016/j.xpro.2022.101866.
short: V. Hübschmann, M. Korkut, S. Siegert, STAR Protocols 3 (2022).
corr_author: '1'
date_created: 2023-01-12T11:56:38Z
date_published: 2022-12-16T00:00:00Z
date_updated: 2025-06-11T13:58:47Z
day: '16'
ddc:
- '570'
department:
- _id: SaSi
- _id: GradSch
doi: 10.1016/j.xpro.2022.101866
ec_funded: 1
external_id:
pmid:
- '36595902'
file:
- access_level: open_access
checksum: 3c71b8a60633d42c2f77c49025d5559b
content_type: application/pdf
creator: dernst
date_created: 2023-01-23T09:50:51Z
date_updated: 2023-01-23T09:50:51Z
file_id: '12340'
file_name: 2022_STARProtocols_Huebschmann.pdf
file_size: 6251945
relation: main_file
success: 1
file_date_updated: 2023-01-23T09:50:51Z
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intvolume: ' 3'
issue: '4'
keyword:
- General Immunology and Microbiology
- General Biochemistry
- Genetics and Molecular Biology
- General Neuroscience
language:
- iso: eng
license: https://creativecommons.org/licenses/by-nc-nd/4.0/
month: '12'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 25D4A630-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '715571'
name: Microglia action towards neuronal circuit formation and function in health
and disease
- _id: 9B99D380-BA93-11EA-9121-9846C619BF3A
grant_number: SC19-017
name: How human microglia shape developing neurons during health and inflammation
publication: STAR Protocols
publication_identifier:
issn:
- 2666-1667
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
record:
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relation: other
status: public
scopus_import: '1'
status: public
title: Assessing human iPSC-derived microglia identity and function by immunostaining,
phagocytosis, calcium activity, and inflammation assay
tmp:
image: /images/cc_by_nc_nd.png
legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
(CC BY-NC-ND 4.0)
short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 3
year: '2022'
...
---
_id: '12244'
abstract:
- lang: eng
text: Environmental cues influence the highly dynamic morphology of microglia. Strategies
to characterize these changes usually involve user-selected morphometric features,
which preclude the identification of a spectrum of context-dependent morphological
phenotypes. Here we develop MorphOMICs, a topological data analysis approach,
which enables semiautomatic mapping of microglial morphology into an atlas of
cue-dependent phenotypes and overcomes feature-selection biases and biological
variability. We extract spatially heterogeneous and sexually dimorphic morphological
phenotypes for seven adult mouse brain regions. This sex-specific phenotype declines
with maturation but increases over the disease trajectories in two neurodegeneration
mouse models, with females showing a faster morphological shift in affected brain
regions. Remarkably, microglia morphologies reflect an adaptation upon repeated
exposure to ketamine anesthesia and do not recover to control morphologies. Finally,
we demonstrate that both long primary processes and short terminal processes provide
distinct insights to morphological phenotypes. MorphOMICs opens a new perspective
to characterize microglial morphology.
acknowledged_ssus:
- _id: PreCl
- _id: Bio
- _id: ScienComp
acknowledgement: We thank the scientific service units at ISTA, in particular M. Schunn’s
team at the preclinical facility, and especially our colony manager S. Haslinger,
for excellent support. We are also grateful to the ISTA Imaging & Optics Facility,
and in particular C. Sommer for helping with the data file conversions. We thank
R. Erhart from the ISTA Scientific Computing Unit for improving the script performance.
We thank M. Maes, B. Nagy, S. Oakeley and M. Benevento and all members of the Siegert
group for constant feedback on the project and on the manuscript. This research
was supported by the European Union Horizon 2020 research and innovation program
under the Marie Skłodowska-Curie Actions program (754411 to R.J.A.C.), and by the
European Research Council (grant no. 715571 to S.S.). L.K. was supported by funding
to the Blue Brain Project, a research center of the École polytechnique fédérale
de Lausanne, from the Swiss government’s ETH Board of the Swiss Federal Institutes
of Technology. L.-H.T. was supported by NIH (grant no. R37NS051874) and by the JPB
Foundation. The funders had no role in study design, data collection and analysis,
decision to publish or preparation of the manuscript.
article_processing_charge: No
article_type: original
author:
- first_name: Gloria
full_name: Colombo, Gloria
id: 3483CF6C-F248-11E8-B48F-1D18A9856A87
last_name: Colombo
orcid: 0000-0001-9434-8902
- first_name: Ryan J
full_name: Cubero, Ryan J
id: 850B2E12-9CD4-11E9-837F-E719E6697425
last_name: Cubero
orcid: 0000-0003-0002-1867
- first_name: Lida
full_name: Kanari, Lida
last_name: Kanari
- first_name: Alessandro
full_name: Venturino, Alessandro
id: 41CB84B2-F248-11E8-B48F-1D18A9856A87
last_name: Venturino
orcid: 0000-0003-2356-9403
- first_name: Rouven
full_name: Schulz, Rouven
id: 4C5E7B96-F248-11E8-B48F-1D18A9856A87
last_name: Schulz
orcid: 0000-0001-5297-733X
- first_name: Martina
full_name: Scolamiero, Martina
last_name: Scolamiero
- first_name: Jens
full_name: Agerberg, Jens
last_name: Agerberg
- first_name: Hansruedi
full_name: Mathys, Hansruedi
last_name: Mathys
- first_name: Li-Huei
full_name: Tsai, Li-Huei
last_name: Tsai
- first_name: Wojciech
full_name: Chachólski, Wojciech
last_name: Chachólski
- first_name: Kathryn
full_name: Hess, Kathryn
last_name: Hess
- first_name: Sandra
full_name: Siegert, Sandra
id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
last_name: Siegert
orcid: 0000-0001-8635-0877
citation:
ama: Colombo G, Cubero RJ, Kanari L, et al. A tool for mapping microglial morphology,
morphOMICs, reveals brain-region and sex-dependent phenotypes. Nature Neuroscience.
2022;25(10):1379-1393. doi:10.1038/s41593-022-01167-6
apa: Colombo, G., Cubero, R. J., Kanari, L., Venturino, A., Schulz, R., Scolamiero,
M., … Siegert, S. (2022). A tool for mapping microglial morphology, morphOMICs,
reveals brain-region and sex-dependent phenotypes. Nature Neuroscience.
Springer Nature. https://doi.org/10.1038/s41593-022-01167-6
chicago: Colombo, Gloria, Ryan J Cubero, Lida Kanari, Alessandro Venturino, Rouven
Schulz, Martina Scolamiero, Jens Agerberg, et al. “A Tool for Mapping Microglial
Morphology, MorphOMICs, Reveals Brain-Region and Sex-Dependent Phenotypes.” Nature
Neuroscience. Springer Nature, 2022. https://doi.org/10.1038/s41593-022-01167-6.
ieee: G. Colombo et al., “A tool for mapping microglial morphology, morphOMICs,
reveals brain-region and sex-dependent phenotypes,” Nature Neuroscience,
vol. 25, no. 10. Springer Nature, pp. 1379–1393, 2022.
ista: Colombo G, Cubero RJ, Kanari L, Venturino A, Schulz R, Scolamiero M, Agerberg
J, Mathys H, Tsai L-H, Chachólski W, Hess K, Siegert S. 2022. A tool for mapping
microglial morphology, morphOMICs, reveals brain-region and sex-dependent phenotypes.
Nature Neuroscience. 25(10), 1379–1393.
mla: Colombo, Gloria, et al. “A Tool for Mapping Microglial Morphology, MorphOMICs,
Reveals Brain-Region and Sex-Dependent Phenotypes.” Nature Neuroscience,
vol. 25, no. 10, Springer Nature, 2022, pp. 1379–93, doi:10.1038/s41593-022-01167-6.
short: G. Colombo, R.J. Cubero, L. Kanari, A. Venturino, R. Schulz, M. Scolamiero,
J. Agerberg, H. Mathys, L.-H. Tsai, W. Chachólski, K. Hess, S. Siegert, Nature
Neuroscience 25 (2022) 1379–1393.
corr_author: '1'
date_created: 2023-01-16T09:53:07Z
date_published: 2022-10-01T00:00:00Z
date_updated: 2026-07-28T22:30:09Z
day: '01'
ddc:
- '570'
department:
- _id: SaSi
doi: 10.1038/s41593-022-01167-6
ec_funded: 1
external_id:
isi:
- '000862214700001'
pmid:
- '36180790'
file:
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creator: dernst
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date_updated: 2023-01-30T08:06:56Z
file_id: '12437'
file_name: 2022_NatureNeuroscience_Colombo.pdf
file_size: 23789835
relation: main_file
success: 1
file_date_updated: 2023-01-30T08:06:56Z
has_accepted_license: '1'
intvolume: ' 25'
isi: 1
issue: '10'
keyword:
- General Neuroscience
language:
- iso: eng
month: '10'
oa: 1
oa_version: Published Version
page: 1379-1393
pmid: 1
project:
- _id: 260C2330-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '754411'
name: ISTplus - Postdoctoral Fellowships
- _id: 25D4A630-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '715571'
name: Microglia action towards neuronal circuit formation and function in health
and disease
publication: Nature Neuroscience
publication_identifier:
eissn:
- 1546-1726
issn:
- 1097-6256
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
link:
- description: News on ISTA website
relation: press_release
url: https://ista.ac.at/en/news/morphomics-revealing-the-hidden-meaning-of-microglia-shape/
record:
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relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: A tool for mapping microglial morphology, morphOMICs, reveals brain-region
and sex-dependent phenotypes
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 25
year: '2022'
...
---
OA_place: publisher
_id: '12378'
abstract:
- lang: eng
text: "Environmental cues influence the highly dynamic morphology of microglia.
Strategies to \r\ncharacterize these changes usually involve user-selected morphometric
features, which \r\npreclude the identification of a spectrum of context-dependent
morphological phenotypes. \r\nHere, we develop MorphOMICs, a topological data
analysis approach, which enables semi\x02automatic mapping of microglial morphology
into an atlas of cue-dependent phenotypes,\r\novercomes feature-selection bias
and minimizes biological variability. \r\nFirst, with MorphOMICs we derive the
morphological spectrum of microglia across seven \r\nbrain regions during postnatal
development and in two distinct Alzheimer’s disease \r\ndegeneration mouse models.
We uncover region-specific and sexually dimorphic\r\nmorphological trajectories,
with females showing an earlier morphological shift than males in \r\nthe degenerating
brain. Overall, we demonstrate that both long primary- and short terminal \r\nprocesses
provide distinct insights to morphological phenotypes. Moreover, using machine
\r\nlearning to map novel condition on the spectrum, we observe that microglia
morphologies \r\nreflect a dose-dependent adaptation upon ketamine anesthesia
and do not recover to control \r\nmorphologies.\r\nNext, we took advantage of
MorphOMICs to build a high-resolution and layer-specific map of \r\nmicroglial
morphological spectrum in the retina, covering postnatal development and rd10
\r\ndegeneration. Here, following photoreceptor death, microglia assume an early
development\x02like morphology. Finally, we map microglial morphology following
optic nerve crush on the \r\nretinal spectrum and observe a layer- and sex-dependent
response. \r\nOverall, MorphOMICs opens a new perspective to analyze microglial
morphology across \r\nmultiple conditions, and provides a novel tool to characterize
microglial morphology beyond \r\nthe traditionally dichotomized view of microglia."
acknowledged_ssus:
- _id: PreCl
- _id: Bio
- _id: ScienComp
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Gloria
full_name: Colombo, Gloria
id: 3483CF6C-F248-11E8-B48F-1D18A9856A87
last_name: Colombo
orcid: 0000-0001-9434-8902
citation:
ama: Colombo G. MorphOMICs, a tool for mapping microglial morphology, reveals brain
region- and sex-dependent phenotypes. 2022. doi:10.15479/at:ista:12378
apa: Colombo, G. (2022). MorphOMICs, a tool for mapping microglial morphology,
reveals brain region- and sex-dependent phenotypes. Institute of Science and
Technology Austria. https://doi.org/10.15479/at:ista:12378
chicago: Colombo, Gloria. “MorphOMICs, a Tool for Mapping Microglial Morphology,
Reveals Brain Region- and Sex-Dependent Phenotypes.” Institute of Science and
Technology Austria, 2022. https://doi.org/10.15479/at:ista:12378.
ieee: G. Colombo, “MorphOMICs, a tool for mapping microglial morphology, reveals
brain region- and sex-dependent phenotypes,” Institute of Science and Technology
Austria, 2022.
ista: Colombo G. 2022. MorphOMICs, a tool for mapping microglial morphology, reveals
brain region- and sex-dependent phenotypes. Institute of Science and Technology
Austria.
mla: Colombo, Gloria. MorphOMICs, a Tool for Mapping Microglial Morphology, Reveals
Brain Region- and Sex-Dependent Phenotypes. Institute of Science and Technology
Austria, 2022, doi:10.15479/at:ista:12378.
short: G. Colombo, MorphOMICs, a Tool for Mapping Microglial Morphology, Reveals
Brain Region- and Sex-Dependent Phenotypes, Institute of Science and Technology
Austria, 2022.
corr_author: '1'
date_created: 2023-01-25T14:27:43Z
date_published: 2022-11-11T00:00:00Z
date_updated: 2026-04-07T14:29:41Z
day: '11'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: GradSch
- _id: SaSi
doi: 10.15479/at:ista:12378
ec_funded: 1
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date_updated: 2023-04-12T22:30:03Z
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file_date_updated: 2023-04-12T22:30:03Z
has_accepted_license: '1'
language:
- iso: eng
month: '11'
oa: 1
oa_version: Published Version
page: '142'
project:
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '665385'
name: International IST Doctoral Program
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '12244'
relation: part_of_dissertation
status: public
status: public
supervisor:
- first_name: Sandra
full_name: Siegert, Sandra
id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
last_name: Siegert
orcid: 0000-0001-8635-0877
title: MorphOMICs, a tool for mapping microglial morphology, reveals brain region-
and sex-dependent phenotypes
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2022'
...
---
_id: '11950'
abstract:
- lang: eng
text: Mapping the complex and dense arrangement of cells and their connectivity
in brain tissue demands nanoscale spatial resolution imaging. Super-resolution
optical microscopy excels at visualizing specific molecules and individual cells
but fails to provide tissue context. Here we developed Comprehensive Analysis
of Tissues across Scales (CATS), a technology to densely map brain tissue architecture
from millimeter regional to nanoscopic synaptic scales in diverse chemically fixed
brain preparations, including rodent and human. CATS leverages fixation-compatible
extracellular labeling and advanced optical readout, in particular stimulated-emission
depletion and expansion microscopy, to comprehensively delineate cellular structures.
It enables 3D-reconstructing single synapses and mapping synaptic connectivity
by identification and tailored analysis of putative synaptic cleft regions. Applying
CATS to the hippocampal mossy fiber circuitry, we demonstrate its power to reveal
the system’s molecularly informed ultrastructure across spatial scales and assess
local connectivity by reconstructing and quantifying the synaptic input and output
structure of identified neurons.
article_processing_charge: No
author:
- first_name: Julia M
full_name: Michalska, Julia M
id: 443DB6DE-F248-11E8-B48F-1D18A9856A87
last_name: Michalska
orcid: 0000-0003-3862-1235
- first_name: Julia
full_name: Lyudchik, Julia
id: 46E28B80-F248-11E8-B48F-1D18A9856A87
last_name: Lyudchik
- first_name: Philipp
full_name: Velicky, Philipp
id: 39BDC62C-F248-11E8-B48F-1D18A9856A87
last_name: Velicky
orcid: 0000-0002-2340-7431
- first_name: Hana
full_name: Korinkova, Hana
id: ee3cb6ca-ec98-11ea-ae11-ff703e2254ed
last_name: Korinkova
- first_name: Jake
full_name: Watson, Jake
id: 63836096-4690-11EA-BD4E-32803DDC885E
last_name: Watson
orcid: 0000-0002-8698-3823
- first_name: Alban
full_name: Cenameri, Alban
id: 9ac8f577-2357-11eb-997a-e566c5550886
last_name: Cenameri
- first_name: Christoph M
full_name: Sommer, Christoph M
id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
last_name: Sommer
orcid: 0000-0003-1216-9105
- first_name: Alessandro
full_name: Venturino, Alessandro
id: 41CB84B2-F248-11E8-B48F-1D18A9856A87
last_name: Venturino
orcid: 0000-0003-2356-9403
- first_name: Karl
full_name: Roessler, Karl
last_name: Roessler
- first_name: Thomas
full_name: Czech, Thomas
last_name: Czech
- first_name: Sandra
full_name: Siegert, Sandra
id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
last_name: Siegert
orcid: 0000-0001-8635-0877
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
- first_name: Peter M
full_name: Jonas, Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
- first_name: Johann G
full_name: Danzl, Johann G
id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
last_name: Danzl
orcid: 0000-0001-8559-3973
citation:
ama: Michalska JM, Lyudchik J, Velicky P, et al. Uncovering brain tissue architecture
across scales with super-resolution light microscopy. bioRxiv. doi:10.1101/2022.08.17.504272
apa: Michalska, J. M., Lyudchik, J., Velicky, P., Korinkova, H., Watson, J., Cenameri,
A., … Danzl, J. G. (n.d.). Uncovering brain tissue architecture across scales
with super-resolution light microscopy. bioRxiv. https://doi.org/10.1101/2022.08.17.504272
chicago: Michalska, Julia M, Julia Lyudchik, Philipp Velicky, Hana Korinkova, Jake
Watson, Alban Cenameri, Christoph M Sommer, et al. “Uncovering Brain Tissue Architecture
across Scales with Super-Resolution Light Microscopy.” BioRxiv, n.d. https://doi.org/10.1101/2022.08.17.504272.
ieee: J. M. Michalska et al., “Uncovering brain tissue architecture across
scales with super-resolution light microscopy,” bioRxiv. .
ista: Michalska JM, Lyudchik J, Velicky P, Korinkova H, Watson J, Cenameri A, Sommer
CM, Venturino A, Roessler K, Czech T, Siegert S, Novarino G, Jonas PM, Danzl JG.
Uncovering brain tissue architecture across scales with super-resolution light
microscopy. bioRxiv, 10.1101/2022.08.17.504272.
mla: Michalska, Julia M., et al. “Uncovering Brain Tissue Architecture across Scales
with Super-Resolution Light Microscopy.” BioRxiv, doi:10.1101/2022.08.17.504272.
short: J.M. Michalska, J. Lyudchik, P. Velicky, H. Korinkova, J. Watson, A. Cenameri,
C.M. Sommer, A. Venturino, K. Roessler, T. Czech, S. Siegert, G. Novarino, P.M.
Jonas, J.G. Danzl, BioRxiv (n.d.).
corr_author: '1'
das_tickbox: '1'
date_created: 2022-08-24T08:24:52Z
date_published: 2022-08-18T00:00:00Z
date_updated: 2026-07-28T22:31:09Z
day: '18'
department:
- _id: SaSi
- _id: GaNo
- _id: PeJo
- _id: JoDa
doi: 10.1101/2022.08.17.504272
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1101/2022.08.17.504272
month: '08'
oa: 1
oa_version: Preprint
publication: bioRxiv
publication_status: draft
related_material:
record:
- id: '12470'
relation: dissertation_contains
status: public
status: public
title: Uncovering brain tissue architecture across scales with super-resolution light
microscopy
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2022'
...
---
_id: '10000'
abstract:
- lang: eng
text: Inhibition or targeted deletion of histone deacetylase 3 (HDAC3) is neuroprotective
in a variety neurodegenerative conditions, including retinal ganglion cells (RGCs)
after acute optic nerve damage. Consistent with this, induced HDAC3 expression
in cultured cells shows selective toxicity to neurons. Despite an established
role for HDAC3 in neuronal pathology, little is known regarding the mechanism
of this pathology.
acknowledgement: 'The authors thank Joel Dietz for maintaining the mice used in this
study, Satoshi Kinoshita and the Translational Research Initiative in Pathology
Laboratory at the University of Wisconsin-Madison for cutting retinal sections analyzed
in this study, and Mark Banghart for statistical review of the data analysis. Supported
by National Eye Institute Grants R01 EY012223 (RWN), R01 EY030123 (RWN), R01 EY029809
(LWG), R01 EY029809 (LWG) and a Vision Research CORE grant P30 EY016665, NRSA grant
T32 GM081061, by an unrestricted research grant from Research to Prevent Blindness,
Inc., and by a University of Wisconsin-Madison Vilas Life Cycle award and the Frederick
A. Davis Research Chair (RWN). '
article_number: '14'
article_processing_charge: Yes
article_type: original
author:
- first_name: Heather M.
full_name: Schmitt, Heather M.
last_name: Schmitt
- first_name: Rachel L.
full_name: Fehrman, Rachel L.
last_name: Fehrman
- first_name: Margaret E
full_name: Maes, Margaret E
id: 3838F452-F248-11E8-B48F-1D18A9856A87
last_name: Maes
orcid: 0000-0001-9642-1085
- first_name: Huan
full_name: Yang, Huan
last_name: Yang
- first_name: Lian Wang
full_name: Guo, Lian Wang
last_name: Guo
- first_name: Cassandra L.
full_name: Schlamp, Cassandra L.
last_name: Schlamp
- first_name: Heather R.
full_name: Pelzel, Heather R.
last_name: Pelzel
- first_name: Robert W.
full_name: Nickells, Robert W.
last_name: Nickells
citation:
ama: Schmitt HM, Fehrman RL, Maes ME, et al. Increased susceptibility and intrinsic
apoptotic signaling in neurons by induced HDAC3 expression. Investigative Ophthalmology
and Visual Science. 2021;62(10). doi:10.1167/IOVS.62.10.14
apa: Schmitt, H. M., Fehrman, R. L., Maes, M. E., Yang, H., Guo, L. W., Schlamp,
C. L., … Nickells, R. W. (2021). Increased susceptibility and intrinsic apoptotic
signaling in neurons by induced HDAC3 expression. Investigative Ophthalmology
and Visual Science. Association for Research in Vision and Ophthalmology.
https://doi.org/10.1167/IOVS.62.10.14
chicago: Schmitt, Heather M., Rachel L. Fehrman, Margaret E Maes, Huan Yang, Lian
Wang Guo, Cassandra L. Schlamp, Heather R. Pelzel, and Robert W. Nickells. “Increased
Susceptibility and Intrinsic Apoptotic Signaling in Neurons by Induced HDAC3 Expression.”
Investigative Ophthalmology and Visual Science. Association for Research
in Vision and Ophthalmology, 2021. https://doi.org/10.1167/IOVS.62.10.14.
ieee: H. M. Schmitt et al., “Increased susceptibility and intrinsic apoptotic
signaling in neurons by induced HDAC3 expression,” Investigative Ophthalmology
and Visual Science, vol. 62, no. 10. Association for Research in Vision and
Ophthalmology, 2021.
ista: Schmitt HM, Fehrman RL, Maes ME, Yang H, Guo LW, Schlamp CL, Pelzel HR, Nickells
RW. 2021. Increased susceptibility and intrinsic apoptotic signaling in neurons
by induced HDAC3 expression. Investigative Ophthalmology and Visual Science. 62(10),
14.
mla: Schmitt, Heather M., et al. “Increased Susceptibility and Intrinsic Apoptotic
Signaling in Neurons by Induced HDAC3 Expression.” Investigative Ophthalmology
and Visual Science, vol. 62, no. 10, 14, Association for Research in Vision
and Ophthalmology, 2021, doi:10.1167/IOVS.62.10.14.
short: H.M. Schmitt, R.L. Fehrman, M.E. Maes, H. Yang, L.W. Guo, C.L. Schlamp, H.R.
Pelzel, R.W. Nickells, Investigative Ophthalmology and Visual Science 62 (2021).
date_created: 2021-09-12T22:01:23Z
date_published: 2021-08-16T00:00:00Z
date_updated: 2023-08-14T06:35:17Z
day: '16'
ddc:
- '570'
department:
- _id: SaSi
doi: 10.1167/IOVS.62.10.14
external_id:
isi:
- '000695230000014'
pmid:
- '34398198'
file:
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checksum: c430967746f653aa1ae84ee617f62b73
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language:
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month: '08'
oa: 1
oa_version: Published Version
pmid: 1
publication: Investigative Ophthalmology and Visual Science
publication_identifier:
eissn:
- 1552-5783
issn:
- 0146-0404
publication_status: published
publisher: Association for Research in Vision and Ophthalmology
quality_controlled: '1'
scopus_import: '1'
status: public
title: Increased susceptibility and intrinsic apoptotic signaling in neurons by induced
HDAC3 expression
tmp:
image: /images/cc_by_nc_nd.png
legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
(CC BY-NC-ND 4.0)
short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 62
year: '2021'
...
---
_id: '10565'
abstract:
- lang: eng
text: 'Enzymatic digestion of the extracellular matrix with chondroitinase-ABC reinstates
juvenile-like plasticity in the adult cortex as it also disassembles the perineuronal
nets (PNNs). The disadvantage of the enzyme is that it must be applied intracerebrally
and it degrades the ECM for several weeks. Here, we provide two minimally invasive
and transient protocols for microglia-enabled PNN disassembly in mouse cortex:
repeated treatment with ketamine-xylazine-acepromazine (KXA) anesthesia and 60-Hz
light entrainment. We also discuss how to analyze PNNs within microglial endosomes-lysosomes.
For complete details on the use and execution of this protocol, please refer to
Venturino et al. (2021).'
acknowledged_ssus:
- _id: Bio
acknowledgement: This research was supported by the European Research Council (grant
715571 to S.S.). We thank Rouven Schulz, Michael Schunn, Claudia Gold, Gabriel Krens,
Sarah Gorkiewicz, Margaret Maes, Jürgen Siegert, Marco Benevento, and Sara Oakeley
for comments on the manuscript and the IST Austria Bioimaging Facility for the technical
support.
article_number: '101012'
article_processing_charge: Yes
article_type: original
author:
- first_name: Alessandro
full_name: Venturino, Alessandro
id: 41CB84B2-F248-11E8-B48F-1D18A9856A87
last_name: Venturino
orcid: 0000-0003-2356-9403
- first_name: Sandra
full_name: Siegert, Sandra
id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
last_name: Siegert
orcid: 0000-0001-8635-0877
citation:
ama: Venturino A, Siegert S. Minimally invasive protocols and quantification for
microglia-mediated perineuronal net disassembly in mouse brain. STAR Protocols.
2021;2(4). doi:10.1016/j.xpro.2021.101012
apa: Venturino, A., & Siegert, S. (2021). Minimally invasive protocols and quantification
for microglia-mediated perineuronal net disassembly in mouse brain. STAR Protocols.
Elsevier. https://doi.org/10.1016/j.xpro.2021.101012
chicago: Venturino, Alessandro, and Sandra Siegert. “Minimally Invasive Protocols
and Quantification for Microglia-Mediated Perineuronal Net Disassembly in Mouse
Brain.” STAR Protocols. Elsevier, 2021. https://doi.org/10.1016/j.xpro.2021.101012.
ieee: A. Venturino and S. Siegert, “Minimally invasive protocols and quantification
for microglia-mediated perineuronal net disassembly in mouse brain,” STAR Protocols,
vol. 2, no. 4. Elsevier, 2021.
ista: Venturino A, Siegert S. 2021. Minimally invasive protocols and quantification
for microglia-mediated perineuronal net disassembly in mouse brain. STAR Protocols.
2(4), 101012.
mla: Venturino, Alessandro, and Sandra Siegert. “Minimally Invasive Protocols and
Quantification for Microglia-Mediated Perineuronal Net Disassembly in Mouse Brain.”
STAR Protocols, vol. 2, no. 4, 101012, Elsevier, 2021, doi:10.1016/j.xpro.2021.101012.
short: A. Venturino, S. Siegert, STAR Protocols 2 (2021).
date_created: 2021-12-19T23:01:32Z
date_published: 2021-12-17T00:00:00Z
date_updated: 2025-05-14T11:26:30Z
day: '17'
ddc:
- '573'
department:
- _id: SaSi
doi: 10.1016/j.xpro.2021.101012
ec_funded: 1
file:
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checksum: 9ea2501056c5df99e84726b845e9b976
content_type: application/pdf
creator: cchlebak
date_created: 2021-12-20T08:58:40Z
date_updated: 2021-12-20T08:58:40Z
file_id: '10570'
file_name: 2021_STARProt_Venturino.pdf
file_size: 6207060
relation: main_file
success: 1
file_date_updated: 2021-12-20T08:58:40Z
has_accepted_license: '1'
intvolume: ' 2'
issue: '4'
language:
- iso: eng
month: '12'
oa: 1
oa_version: Published Version
project:
- _id: 25D4A630-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '715571'
name: Microglia action towards neuronal circuit formation and function in health
and disease
publication: STAR Protocols
publication_identifier:
eissn:
- 2666-1667
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: Minimally invasive protocols and quantification for microglia-mediated perineuronal
net disassembly in mouse brain
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 2
year: '2021'
...