---
_id: '3'
abstract:
- lang: eng
text: SETD5 gene mutations have been identified as a frequent cause of idiopathic
intellectual disability. Here we show that Setd5-haploinsufficient mice present
developmental defects such as abnormal brain-to-body weight ratios and neural
crest defect-associated phenotypes. Furthermore, Setd5-mutant mice show impairments
in cognitive tasks, enhanced long-term potentiation, delayed ontogenetic profile
of ultrasonic vocalization, and behavioral inflexibility. Behavioral issues are
accompanied by abnormal expression of postsynaptic density proteins previously
associated with cognition. Our data additionally indicate that Setd5 regulates
RNA polymerase II dynamics and gene transcription via its interaction with the
Hdac3 and Paf1 complexes, findings potentially explaining the gene expression
defects observed in Setd5-haploinsufficient mice. Our results emphasize the decisive
role of Setd5 in a biological pathway found to be disrupted in humans with intellectual
disability and autism spectrum disorder.
acknowledged_ssus:
- _id: M-Shop
- _id: PreCl
acknowledgement: This work was supported by the Simons Foundation Autism Research
Initiative (grant 401299) to G.N. and the DFG (SPP1738 grant NO 1249) to K.-M.N.
article_processing_charge: No
article_type: original
author:
- first_name: Elena
full_name: Deliu, Elena
id: 37A40D7E-F248-11E8-B48F-1D18A9856A87
last_name: Deliu
orcid: 0000-0002-7370-5293
- first_name: Niccoló
full_name: Arecco, Niccoló
last_name: Arecco
- first_name: Jasmin
full_name: Morandell, Jasmin
id: 4739D480-F248-11E8-B48F-1D18A9856A87
last_name: Morandell
- first_name: Christoph
full_name: Dotter, Christoph
id: 4C66542E-F248-11E8-B48F-1D18A9856A87
last_name: Dotter
orcid: 0000-0002-9033-9096
- first_name: Ximena
full_name: Contreras, Ximena
id: 475990FE-F248-11E8-B48F-1D18A9856A87
last_name: Contreras
- first_name: Charles
full_name: Girardot, Charles
last_name: Girardot
- first_name: Eva
full_name: Käsper, Eva
last_name: Käsper
- first_name: Alena
full_name: Kozlova, Alena
id: C50A9596-02D0-11E9-976E-E38CFE5CBC1D
last_name: Kozlova
- first_name: Kasumi
full_name: Kishi, Kasumi
id: 3065DFC4-F248-11E8-B48F-1D18A9856A87
last_name: Kishi
- first_name: Ilaria
full_name: Chiaradia, Ilaria
id: B6467F20-02D0-11E9-BDA5-E960C241894A
last_name: Chiaradia
orcid: 0000-0002-9529-4464
- first_name: Kyung
full_name: Noh, Kyung
last_name: Noh
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
citation:
ama: Deliu E, Arecco N, Morandell J, et al. Haploinsufficiency of the intellectual
disability gene SETD5 disturbs developmental gene expression and cognition. Nature
Neuroscience. 2018;21(12):1717-1727. doi:10.1038/s41593-018-0266-2
apa: Deliu, E., Arecco, N., Morandell, J., Dotter, C., Contreras, X., Girardot,
C., … Novarino, G. (2018). Haploinsufficiency of the intellectual disability gene
SETD5 disturbs developmental gene expression and cognition. Nature Neuroscience.
Nature Publishing Group. https://doi.org/10.1038/s41593-018-0266-2
chicago: Deliu, Elena, Niccoló Arecco, Jasmin Morandell, Christoph Dotter, Ximena
Contreras, Charles Girardot, Eva Käsper, et al. “Haploinsufficiency of the Intellectual
Disability Gene SETD5 Disturbs Developmental Gene Expression and Cognition.” Nature
Neuroscience. Nature Publishing Group, 2018. https://doi.org/10.1038/s41593-018-0266-2.
ieee: E. Deliu et al., “Haploinsufficiency of the intellectual disability
gene SETD5 disturbs developmental gene expression and cognition,” Nature Neuroscience,
vol. 21, no. 12. Nature Publishing Group, pp. 1717–1727, 2018.
ista: Deliu E, Arecco N, Morandell J, Dotter C, Contreras X, Girardot C, Käsper
E, Kozlova A, Kishi K, Chiaradia I, Noh K, Novarino G. 2018. Haploinsufficiency
of the intellectual disability gene SETD5 disturbs developmental gene expression
and cognition. Nature Neuroscience. 21(12), 1717–1727.
mla: Deliu, Elena, et al. “Haploinsufficiency of the Intellectual Disability Gene
SETD5 Disturbs Developmental Gene Expression and Cognition.” Nature Neuroscience,
vol. 21, no. 12, Nature Publishing Group, 2018, pp. 1717–27, doi:10.1038/s41593-018-0266-2.
short: E. Deliu, N. Arecco, J. Morandell, C. Dotter, X. Contreras, C. Girardot,
E. Käsper, A. Kozlova, K. Kishi, I. Chiaradia, K. Noh, G. Novarino, Nature Neuroscience
21 (2018) 1717–1727.
date_created: 2018-12-11T11:44:05Z
date_published: 2018-11-19T00:00:00Z
date_updated: 2024-03-27T23:30:44Z
day: '19'
ddc:
- '570'
department:
- _id: GaNo
- _id: EdHa
doi: 10.1038/s41593-018-0266-2
external_id:
isi:
- '000451324700010'
file:
- access_level: open_access
checksum: 60abd0f05b7cdc08a6b0ec460884084f
content_type: application/pdf
creator: dernst
date_created: 2019-04-09T07:41:57Z
date_updated: 2020-07-14T12:45:58Z
file_id: '6255'
file_name: 2017_NatureNeuroscience_Deliu.pdf
file_size: 8167169
relation: main_file
file_date_updated: 2020-07-14T12:45:58Z
has_accepted_license: '1'
intvolume: ' 21'
isi: 1
issue: '12'
language:
- iso: eng
month: '11'
oa: 1
oa_version: Submitted Version
page: 1717 - 1727
project:
- _id: 254BA948-B435-11E9-9278-68D0E5697425
grant_number: '401299'
name: Probing development and reversibility of autism spectrum disorders
publication: Nature Neuroscience
publication_status: published
publisher: Nature Publishing Group
publist_id: '8054'
pubrep_id: '1071'
quality_controlled: '1'
related_material:
link:
- description: News on IST Homepage
relation: press_release
url: https://ist.ac.at/en/news/mutation-that-causes-autism-and-intellectual-disability-makes-brain-less-flexible/
record:
- id: '6074'
relation: popular_science
status: public
- id: '12364'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental
gene expression and cognition
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 21
year: '2018'
...
---
_id: '529'
abstract:
- lang: eng
text: The pituitary adenylyl cyclase-activating polypeptide (PACAP) and its G protein-coupled
receptors, PAC1, VPAC1 and VPAC2 form a system involved in a variety of biological
processes. Although some sympathetic stimulatory effects of this system have been
reported, its central cardiovascular regulatory properties are poorly characterized.
VPAC1 receptors are expressed in the nucleus ambiguus (nAmb), a key center controlling
cardiac parasympathetic tone. In this study, we report that selective VPAC1 activation
in rhodamine-labeled cardiac vagal preganglionic neurons of the rat nAmb produces
inositol 1,4,5-trisphosphate receptor-mediated Ca2+ mobilization, membrane depolarization
and activation of P/Q-type Ca2+ channels. In vivo, this pathway converges onto
transient reduction in heart rate of conscious rats. Therefore we demonstrate
a VPAC1-dependent mechanism in the central parasympathetic regulation of the heart
rate, adding to the complexity of PACAP-mediated cardiovascular modulation.
acknowledgement: This study was supported by startup funds from the Jefferson College
of Pharmacy, and by the National Institutes of Health DA023204 (to M.E.A) and P30
DA 013429 to Center for Substance Abuse Research, Temple University.
author:
- first_name: Florin
full_name: Gherghina, Florin L
last_name: Gherghina
- first_name: Andrei
full_name: Tica, Andrei A
last_name: Tica
- first_name: Elena
full_name: Elena Deliu
id: 37A40D7E-F248-11E8-B48F-1D18A9856A87
last_name: Deliu
orcid: 0000-0002-7370-5293
- first_name: Mary
full_name: Abood, Mary E
last_name: Abood
- first_name: G.
full_name: Brailoiu, G. Christina
last_name: Brailoiu
- first_name: Eugen
full_name: Brǎiloiu, Eugen
last_name: Brǎiloiu
citation:
ama: Gherghina F, Tica A, Deliu E, Abood M, Brailoiu G, Brǎiloiu E. Effects of VPAC1
activation in nucleus ambiguus neurons. Brain Research. 2017;1657:297-303.
doi:10.1016/j.brainres.2016.12.026
apa: Gherghina, F., Tica, A., Deliu, E., Abood, M., Brailoiu, G., & Brǎiloiu,
E. (2017). Effects of VPAC1 activation in nucleus ambiguus neurons. Brain Research.
Elsevier. https://doi.org/10.1016/j.brainres.2016.12.026
chicago: Gherghina, Florin, Andrei Tica, Elena Deliu, Mary Abood, G. Brailoiu, and
Eugen Brǎiloiu. “Effects of VPAC1 Activation in Nucleus Ambiguus Neurons.” Brain
Research. Elsevier, 2017. https://doi.org/10.1016/j.brainres.2016.12.026.
ieee: F. Gherghina, A. Tica, E. Deliu, M. Abood, G. Brailoiu, and E. Brǎiloiu, “Effects
of VPAC1 activation in nucleus ambiguus neurons,” Brain Research, vol.
1657. Elsevier, pp. 297–303, 2017.
ista: Gherghina F, Tica A, Deliu E, Abood M, Brailoiu G, Brǎiloiu E. 2017. Effects
of VPAC1 activation in nucleus ambiguus neurons. Brain Research. 1657, 297–303.
mla: Gherghina, Florin, et al. “Effects of VPAC1 Activation in Nucleus Ambiguus
Neurons.” Brain Research, vol. 1657, Elsevier, 2017, pp. 297–303, doi:10.1016/j.brainres.2016.12.026.
short: F. Gherghina, A. Tica, E. Deliu, M. Abood, G. Brailoiu, E. Brǎiloiu, Brain
Research 1657 (2017) 297–303.
date_created: 2018-12-11T11:46:59Z
date_published: 2017-02-15T00:00:00Z
date_updated: 2021-01-12T08:01:26Z
day: '15'
doi: 10.1016/j.brainres.2016.12.026
extern: 1
intvolume: ' 1657'
month: '02'
page: 297 - 303
publication: Brain Research
publication_status: published
publisher: Elsevier
publist_id: '7290'
quality_controlled: 0
status: public
title: Effects of VPAC1 activation in nucleus ambiguus neurons
type: journal_article
volume: 1657
year: '2017'
...
---
_id: '634'
abstract:
- lang: eng
text: As autism spectrum disorder (ASD) is largely regarded as a neurodevelopmental
condition, long-time consensus was that its hallmark features are irreversible.
However, several studies from recent years using defined mouse models of ASD have
provided clear evidence that in mice neurobiological and behavioural alterations
can be ameliorated or even reversed by genetic restoration or pharmacological
treatment either before or after symptom onset. Here, we review findings on genetic
and pharmacological reversibility of phenotypes in mouse models of ASD. Our review
should give a comprehensive overview on both aspects and encourage future studies
to better understand the underlying molecular mechanisms that might be translatable
from animals to humans.
alternative_title:
- ADVSANAT
author:
- first_name: Jan
full_name: Schroeder, Jan
last_name: Schroeder
- first_name: Elena
full_name: Deliu, Elena
id: 37A40D7E-F248-11E8-B48F-1D18A9856A87
last_name: Deliu
orcid: 0000-0002-7370-5293
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
- first_name: Michael
full_name: Schmeisser, Michael
last_name: Schmeisser
citation:
ama: 'Schroeder J, Deliu E, Novarino G, Schmeisser M. Genetic and pharmacological
reversibility of phenotypes in mouse models of autism spectrum disorder. In: Schmeisser
M, Boekers T, eds. Translational Anatomy and Cell Biology of Autism Spectrum
Disorder. Vol 224. Advances in Anatomy Embryology and Cell Biology. Springer;
2017:189-211. doi:10.1007/978-3-319-52498-6_10'
apa: Schroeder, J., Deliu, E., Novarino, G., & Schmeisser, M. (2017). Genetic
and pharmacological reversibility of phenotypes in mouse models of autism spectrum
disorder. In M. Schmeisser & T. Boekers (Eds.), Translational Anatomy and
Cell Biology of Autism Spectrum Disorder (Vol. 224, pp. 189–211). Springer.
https://doi.org/10.1007/978-3-319-52498-6_10
chicago: Schroeder, Jan, Elena Deliu, Gaia Novarino, and Michael Schmeisser. “Genetic
and Pharmacological Reversibility of Phenotypes in Mouse Models of Autism Spectrum
Disorder.” In Translational Anatomy and Cell Biology of Autism Spectrum Disorder,
edited by Michael Schmeisser and Tobias Boekers, 224:189–211. Advances in Anatomy
Embryology and Cell Biology. Springer, 2017. https://doi.org/10.1007/978-3-319-52498-6_10.
ieee: J. Schroeder, E. Deliu, G. Novarino, and M. Schmeisser, “Genetic and pharmacological
reversibility of phenotypes in mouse models of autism spectrum disorder,” in Translational
Anatomy and Cell Biology of Autism Spectrum Disorder, vol. 224, M. Schmeisser
and T. Boekers, Eds. Springer, 2017, pp. 189–211.
ista: 'Schroeder J, Deliu E, Novarino G, Schmeisser M. 2017.Genetic and pharmacological
reversibility of phenotypes in mouse models of autism spectrum disorder. In: Translational
Anatomy and Cell Biology of Autism Spectrum Disorder. ADVSANAT, vol. 224, 189–211.'
mla: Schroeder, Jan, et al. “Genetic and Pharmacological Reversibility of Phenotypes
in Mouse Models of Autism Spectrum Disorder.” Translational Anatomy and Cell
Biology of Autism Spectrum Disorder, edited by Michael Schmeisser and Tobias
Boekers, vol. 224, Springer, 2017, pp. 189–211, doi:10.1007/978-3-319-52498-6_10.
short: J. Schroeder, E. Deliu, G. Novarino, M. Schmeisser, in:, M. Schmeisser, T.
Boekers (Eds.), Translational Anatomy and Cell Biology of Autism Spectrum Disorder,
Springer, 2017, pp. 189–211.
date_created: 2018-12-11T11:47:37Z
date_published: 2017-05-28T00:00:00Z
date_updated: 2021-01-12T08:07:08Z
day: '28'
department:
- _id: GaNo
doi: 10.1007/978-3-319-52498-6_10
editor:
- first_name: Michael
full_name: Schmeisser, Michael
last_name: Schmeisser
- first_name: Tobias
full_name: Boekers, Tobias
last_name: Boekers
intvolume: ' 224'
language:
- iso: eng
month: '05'
oa_version: None
page: 189 - 211
project:
- _id: 25473368-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: F03523
name: Transmembrane Transporters in Health and Disease
publication: Translational Anatomy and Cell Biology of Autism Spectrum Disorder
publication_identifier:
eisbn:
- 978-3-319-52498-6
publication_status: published
publisher: Springer
publist_id: '7156'
quality_controlled: '1'
scopus_import: 1
series_title: Advances in Anatomy Embryology and Cell Biology
status: public
title: Genetic and pharmacological reversibility of phenotypes in mouse models of
autism spectrum disorder
type: book_chapter
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 224
year: '2017'
...
---
_id: '714'
abstract:
- lang: eng
text: Background HIV-1 infection and drug abuse are frequently co-morbid and their
association greatly increases the severity of HIV-1-induced neuropathology. While
nucleus accumbens (NAcc) function is severely perturbed by drugs of abuse, little
is known about how HIV-1 infection affects NAcc. Methods We used calcium and voltage
imaging to investigate the effect of HIV-1 trans-activator of transcription (Tat)
on rat NAcc. Based on previous neuronal studies, we hypothesized that Tat modulates
intracellular Ca2+ homeostasis of NAcc neurons. Results We provide evidence that
Tat triggers a Ca2+ signaling cascade in NAcc medium spiny neurons (MSN) expressing
D1-like dopamine receptors leading to neuronal depolarization. Firstly, Tat induced
inositol 1,4,5-trisphsophate (IP3) receptor-mediated Ca2+ release from endoplasmic
reticulum, followed by Ca2+ and Na+ influx via transient receptor potential canonical
channels. The influx of cations depolarizes the membrane promoting additional
Ca2+ entry through voltage-gated P/Q-type Ca2+ channels and opening of tetrodotoxin-sensitive
Na+ channels. By activating this mechanism, Tat elicits a feed-forward depolarization
increasing the excitability of D1-phosphatidylinositol-linked NAcc MSN. We previously
found that cocaine targets NAcc neurons directly (independent of the inhibition
of dopamine transporter) only when IP3-generating mechanisms are concomitantly
initiated. When tested here, cocaine produced a dose-dependent potentiation of
the effect of Tat on cytosolic Ca2+. Conclusion We describe for the first time
a HIV-1 Tat-triggered Ca2+ signaling in MSN of NAcc involving TRPC and depolarization
and a potentiation of the effect of Tat by cocaine, which may be relevant for
the reward axis in cocaine-abusing HIV-1-positive patients.
acknowledgement: This work was supported by the National Institutes of Health grants
DA035926 (to MEA), and P30DA013429 (to EMU).
article_processing_charge: No
article_type: original
author:
- first_name: Gabriela
full_name: Brailoiu, Gabriela
last_name: Brailoiu
- first_name: Elena
full_name: Deliu, Elena
id: 37A40D7E-F248-11E8-B48F-1D18A9856A87
last_name: Deliu
orcid: 0000-0002-7370-5293
- first_name: Jeffrey
full_name: Barr, Jeffrey
last_name: Barr
- first_name: Linda
full_name: Console Bram, Linda
last_name: Console Bram
- first_name: Alexandra
full_name: Ciuciu, Alexandra
last_name: Ciuciu
- first_name: Mary
full_name: Abood, Mary
last_name: Abood
- first_name: Ellen
full_name: Unterwald, Ellen
last_name: Unterwald
- first_name: Eugen
full_name: Brǎiloiu, Eugen
last_name: Brǎiloiu
citation:
ama: Brailoiu G, Deliu E, Barr J, et al. HIV Tat excites D1 receptor-like expressing
neurons from rat nucleus accumbens. Drug and Alcohol Dependence. 2017;178:7-14.
doi:10.1016/j.drugalcdep.2017.04.015
apa: Brailoiu, G., Deliu, E., Barr, J., Console Bram, L., Ciuciu, A., Abood, M.,
… Brǎiloiu, E. (2017). HIV Tat excites D1 receptor-like expressing neurons from
rat nucleus accumbens. Drug and Alcohol Dependence. Elsevier. https://doi.org/10.1016/j.drugalcdep.2017.04.015
chicago: Brailoiu, Gabriela, Elena Deliu, Jeffrey Barr, Linda Console Bram, Alexandra
Ciuciu, Mary Abood, Ellen Unterwald, and Eugen Brǎiloiu. “HIV Tat Excites D1 Receptor-like
Expressing Neurons from Rat Nucleus Accumbens.” Drug and Alcohol Dependence.
Elsevier, 2017. https://doi.org/10.1016/j.drugalcdep.2017.04.015.
ieee: G. Brailoiu et al., “HIV Tat excites D1 receptor-like expressing neurons
from rat nucleus accumbens,” Drug and Alcohol Dependence, vol. 178. Elsevier,
pp. 7–14, 2017.
ista: Brailoiu G, Deliu E, Barr J, Console Bram L, Ciuciu A, Abood M, Unterwald
E, Brǎiloiu E. 2017. HIV Tat excites D1 receptor-like expressing neurons from
rat nucleus accumbens. Drug and Alcohol Dependence. 178, 7–14.
mla: Brailoiu, Gabriela, et al. “HIV Tat Excites D1 Receptor-like Expressing Neurons
from Rat Nucleus Accumbens.” Drug and Alcohol Dependence, vol. 178, Elsevier,
2017, pp. 7–14, doi:10.1016/j.drugalcdep.2017.04.015.
short: G. Brailoiu, E. Deliu, J. Barr, L. Console Bram, A. Ciuciu, M. Abood, E.
Unterwald, E. Brǎiloiu, Drug and Alcohol Dependence 178 (2017) 7–14.
date_created: 2018-12-11T11:48:05Z
date_published: 2017-09-01T00:00:00Z
date_updated: 2021-01-12T08:12:00Z
day: '01'
department:
- _id: GaNo
doi: 10.1016/j.drugalcdep.2017.04.015
external_id:
pmid:
- '28623807'
intvolume: ' 178'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5797705
month: '09'
oa: 1
oa_version: Submitted Version
page: 7 - 14
pmid: 1
publication: Drug and Alcohol Dependence
publication_identifier:
issn:
- '03768716'
publication_status: published
publisher: Elsevier
publist_id: '6967'
quality_controlled: '1'
scopus_import: 1
status: public
title: HIV Tat excites D1 receptor-like expressing neurons from rat nucleus accumbens
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 178
year: '2017'
...
---
_id: '747'
abstract:
- lang: eng
text: Bradykinin (BK), a component of the kallikrein-kininogen-kinin system exerts
multiple effects via B1 and B2 receptor activation. In the cardiovascular system,
bradykinin has cardioprotective and vasodilator properties. We investigated the
effect of BK on cardiac-projecting neurons of nucleus ambiguus, a key site for
the parasympathetic cardiac regulation. BK produced a dose-dependent increase
in cytosolic Ca2+ concentration. Pretreatment with HOE140, a B2 receptor antagonist,
but not with R715, a B1 receptor antagonist, abolished the response to BK. A selective
B2 receptor agonist, but not a B1 receptor agonist, elicited an increase in cytosolic
Ca2+ similarly to BK. Inhibition of N-type voltage-gated Ca2+ channels with ω-conotoxin
GVIA had no effect on the Ca2+ signal produced by BK, while pretreatment with
ω-conotoxin MVIIC, a blocker of P/Q-type of Ca2+ channels, significantly diminished
the effect of BK. Pretreatment with xestospongin C and 2-aminoethoxydiphenyl borate,
antagonists of inositol 1,4,5-trisphosphate receptors, abolished the response
to BK. Inhibition of ryanodine receptors reduced the BK-induced Ca2+ increase,
while disruption of lysosomal Ca2+ stores with bafilomycin A1 did not affect the
response. BK produced a dose-dependent depolarization of nucleus ambiguus neurons,
which was prevented by the B2 receptor antagonist. In vivo studies indicate that
microinjection of BK into nucleus ambiguus elicited bradycardia in conscious rats
via B2 receptors. In summary, in cardiac vagal neurons of nucleus ambiguus, BK
activates B2 receptors promoting Ca2+ influx and Ca2+ release from endoplasmic
reticulum, and membrane depolarization; these effects are translated in vivo by
bradycardia.
article_processing_charge: No
article_type: original
author:
- first_name: Eugen
full_name: Brǎiloiu, Eugen
last_name: Brǎiloiu
- first_name: Matthew
full_name: Mcguire, Matthew
last_name: Mcguire
- first_name: Shadaria
full_name: Shuler, Shadaria
last_name: Shuler
- first_name: Elena
full_name: Deliu, Elena
id: 37A40D7E-F248-11E8-B48F-1D18A9856A87
last_name: Deliu
orcid: 0000-0002-7370-5293
- first_name: Jeffrey
full_name: Barr, Jeffrey
last_name: Barr
- first_name: Mary
full_name: Abood, Mary
last_name: Abood
- first_name: Gabriela
full_name: Brailoiu, Gabriela
last_name: Brailoiu
citation:
ama: Brǎiloiu E, Mcguire M, Shuler S, et al. Modulation of cardiac vagal tone by
bradykinin acting on nucleus ambiguus. Neuroscience. 2017;365:23-32. doi:10.1016/j.neuroscience.2017.09.034
apa: Brǎiloiu, E., Mcguire, M., Shuler, S., Deliu, E., Barr, J., Abood, M., &
Brailoiu, G. (2017). Modulation of cardiac vagal tone by bradykinin acting on
nucleus ambiguus. Neuroscience. Elsevier. https://doi.org/10.1016/j.neuroscience.2017.09.034
chicago: Brǎiloiu, Eugen, Matthew Mcguire, Shadaria Shuler, Elena Deliu, Jeffrey
Barr, Mary Abood, and Gabriela Brailoiu. “Modulation of Cardiac Vagal Tone by
Bradykinin Acting on Nucleus Ambiguus.” Neuroscience. Elsevier, 2017. https://doi.org/10.1016/j.neuroscience.2017.09.034.
ieee: E. Brǎiloiu et al., “Modulation of cardiac vagal tone by bradykinin
acting on nucleus ambiguus,” Neuroscience, vol. 365. Elsevier, pp. 23–32,
2017.
ista: Brǎiloiu E, Mcguire M, Shuler S, Deliu E, Barr J, Abood M, Brailoiu G. 2017.
Modulation of cardiac vagal tone by bradykinin acting on nucleus ambiguus. Neuroscience.
365, 23–32.
mla: Brǎiloiu, Eugen, et al. “Modulation of Cardiac Vagal Tone by Bradykinin Acting
on Nucleus Ambiguus.” Neuroscience, vol. 365, Elsevier, 2017, pp. 23–32,
doi:10.1016/j.neuroscience.2017.09.034.
short: E. Brǎiloiu, M. Mcguire, S. Shuler, E. Deliu, J. Barr, M. Abood, G. Brailoiu,
Neuroscience 365 (2017) 23–32.
date_created: 2018-12-11T11:48:17Z
date_published: 2017-12-04T00:00:00Z
date_updated: 2023-09-27T12:26:59Z
day: '04'
department:
- _id: GaNo
doi: 10.1016/j.neuroscience.2017.09.034
external_id:
isi:
- '000415966200003'
pmid:
- '28951324'
intvolume: ' 365'
isi: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5798458
month: '12'
oa: 1
oa_version: Submitted Version
page: 23 - 32
pmid: 1
publication: Neuroscience
publication_identifier:
issn:
- '03064522'
publication_status: published
publisher: Elsevier
publist_id: '6911'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Modulation of cardiac vagal tone by bradykinin acting on nucleus ambiguus
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 365
year: '2017'
...
---
_id: '1183'
abstract:
- lang: eng
text: Autism spectrum disorders (ASD) are a group of genetic disorders often overlapping
with other neurological conditions. We previously described abnormalities in the
branched-chain amino acid (BCAA) catabolic pathway as a cause of ASD. Here, we
show that the solute carrier transporter 7a5 (SLC7A5), a large neutral amino acid
transporter localized at the blood brain barrier (BBB), has an essential role
in maintaining normal levels of brain BCAAs. In mice, deletion of Slc7a5 from
the endothelial cells of the BBB leads to atypical brain amino acid profile, abnormal
mRNA translation, and severe neurological abnormalities. Furthermore, we identified
several patients with autistic traits and motor delay carrying deleterious homozygous
mutations in the SLC7A5 gene. Finally, we demonstrate that BCAA intracerebroventricular
administration ameliorates abnormal behaviors in adult mutant mice. Our data elucidate
a neurological syndrome defined by SLC7A5 mutations and support an essential role
for the BCAA in human brain function.
acknowledgement: "This work was supported by NICHD (P01HD070494) and SFARI (grant
275275) to J.G.G., and FWF (SFB35_3523) to G.N.\r\nWe thank A.C. Manzano, Mike Liu,
and F. Marr for technical assistance, and R. Shigemoto and the IST Austria Electron
Microscopy (EM) Facility for assistance. We acknowledge support from CIDR for genome-wide
SNP analysis (X01HG008823) and Broad Institute Center for Mendelian Disorders (UM1HG008900
to D. MacArthur), the Yale Center for Mendelian Disorders (U54HG006504 to M.G.),
the Gregory M. Kiez and Mehmet Kutman Foundation (M.G.), Italian Ministry of Instruction
University and Research (PON01_00937 to C.I.), and NIH (R01-GM108911 to A.S.). This
work was supported by NICHD (P01HD070494) and SFARI (grant 275275) to J.G.G., and
FWF (SFB35_3523) to G.N.\r\n\r\n#EMFacility"
article_processing_charge: No
article_type: original
author:
- first_name: Dora-Clara
full_name: Tarlungeanu, Dora-Clara
id: 2ABCE612-F248-11E8-B48F-1D18A9856A87
last_name: Tarlungeanu
- first_name: Elena
full_name: Deliu, Elena
id: 37A40D7E-F248-11E8-B48F-1D18A9856A87
last_name: Deliu
orcid: 0000-0002-7370-5293
- first_name: Christoph
full_name: Dotter, Christoph
id: 4C66542E-F248-11E8-B48F-1D18A9856A87
last_name: Dotter
orcid: 0000-0002-9033-9096
- first_name: Majdi
full_name: Kara, Majdi
last_name: Kara
- first_name: Philipp
full_name: Janiesch, Philipp
last_name: Janiesch
- first_name: Mariafrancesca
full_name: Scalise, Mariafrancesca
last_name: Scalise
- first_name: Michele
full_name: Galluccio, Michele
last_name: Galluccio
- first_name: Mateja
full_name: Tesulov, Mateja
last_name: Tesulov
- first_name: Emanuela
full_name: Morelli, Emanuela
id: 3F4D1282-F248-11E8-B48F-1D18A9856A87
last_name: Morelli
- first_name: Fatma
full_name: Sönmez, Fatma
last_name: Sönmez
- first_name: Kaya
full_name: Bilgüvar, Kaya
last_name: Bilgüvar
- first_name: Ryuichi
full_name: Ohgaki, Ryuichi
last_name: Ohgaki
- first_name: Yoshikatsu
full_name: Kanai, Yoshikatsu
last_name: Kanai
- first_name: Anide
full_name: Johansen, Anide
last_name: Johansen
- first_name: Seham
full_name: Esharif, Seham
last_name: Esharif
- first_name: Tawfeg
full_name: Ben Omran, Tawfeg
last_name: Ben Omran
- first_name: Meral
full_name: Topcu, Meral
last_name: Topcu
- first_name: Avner
full_name: Schlessinger, Avner
last_name: Schlessinger
- first_name: Cesare
full_name: Indiveri, Cesare
last_name: Indiveri
- first_name: Kent
full_name: Duncan, Kent
last_name: Duncan
- first_name: Ahmet
full_name: Caglayan, Ahmet
last_name: Caglayan
- first_name: Murat
full_name: Günel, Murat
last_name: Günel
- first_name: Joseph
full_name: Gleeson, Joseph
last_name: Gleeson
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
citation:
ama: Tarlungeanu D-C, Deliu E, Dotter C, et al. Impaired amino acid transport at
the blood brain barrier is a cause of autism spectrum disorder. Cell. 2016;167(6):1481-1494.
doi:10.1016/j.cell.2016.11.013
apa: Tarlungeanu, D.-C., Deliu, E., Dotter, C., Kara, M., Janiesch, P., Scalise,
M., … Novarino, G. (2016). Impaired amino acid transport at the blood brain barrier
is a cause of autism spectrum disorder. Cell. Cell Press. https://doi.org/10.1016/j.cell.2016.11.013
chicago: Tarlungeanu, Dora-Clara, Elena Deliu, Christoph Dotter, Majdi Kara, Philipp
Janiesch, Mariafrancesca Scalise, Michele Galluccio, et al. “Impaired Amino Acid
Transport at the Blood Brain Barrier Is a Cause of Autism Spectrum Disorder.”
Cell. Cell Press, 2016. https://doi.org/10.1016/j.cell.2016.11.013.
ieee: D.-C. Tarlungeanu et al., “Impaired amino acid transport at the blood
brain barrier is a cause of autism spectrum disorder,” Cell, vol. 167,
no. 6. Cell Press, pp. 1481–1494, 2016.
ista: Tarlungeanu D-C, Deliu E, Dotter C, Kara M, Janiesch P, Scalise M, Galluccio
M, Tesulov M, Morelli E, Sönmez F, Bilgüvar K, Ohgaki R, Kanai Y, Johansen A,
Esharif S, Ben Omran T, Topcu M, Schlessinger A, Indiveri C, Duncan K, Caglayan
A, Günel M, Gleeson J, Novarino G. 2016. Impaired amino acid transport at the
blood brain barrier is a cause of autism spectrum disorder. Cell. 167(6), 1481–1494.
mla: Tarlungeanu, Dora-Clara, et al. “Impaired Amino Acid Transport at the Blood
Brain Barrier Is a Cause of Autism Spectrum Disorder.” Cell, vol. 167,
no. 6, Cell Press, 2016, pp. 1481–94, doi:10.1016/j.cell.2016.11.013.
short: D.-C. Tarlungeanu, E. Deliu, C. Dotter, M. Kara, P. Janiesch, M. Scalise,
M. Galluccio, M. Tesulov, E. Morelli, F. Sönmez, K. Bilgüvar, R. Ohgaki, Y. Kanai,
A. Johansen, S. Esharif, T. Ben Omran, M. Topcu, A. Schlessinger, C. Indiveri,
K. Duncan, A. Caglayan, M. Günel, J. Gleeson, G. Novarino, Cell 167 (2016) 1481–1494.
date_created: 2018-12-11T11:50:35Z
date_published: 2016-12-01T00:00:00Z
date_updated: 2024-03-27T23:30:12Z
day: '01'
ddc:
- '576'
- '616'
department:
- _id: GaNo
doi: 10.1016/j.cell.2016.11.013
file:
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checksum: 7fe01ab12a6610d3db421e0136db2f77
content_type: application/pdf
creator: system
date_created: 2018-12-12T10:13:44Z
date_updated: 2020-07-14T12:44:37Z
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file_name: IST-2017-771-v1+1_Tarlungeanu_et_al._Final_edited.pdf
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language:
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page: 1481 - 1494
project:
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call_identifier: FWF
grant_number: F03523
name: Transmembrane Transporters in Health and Disease
publication: Cell
publication_status: published
publisher: Cell Press
publist_id: '6170'
pubrep_id: '771'
quality_controlled: '1'
related_material:
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scopus_import: '1'
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title: Impaired amino acid transport at the blood brain barrier is a cause of autism
spectrum disorder
type: journal_article
user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9
volume: 167
year: '2016'
...