---
OA_place: publisher
OA_type: hybrid
PlanS_conform: '1'
_id: '21860'
abstract:
- lang: eng
  text: Glutamate excitotoxicity is a cell death mechanism triggered by accumulation
    of glutamate in the extracellular space. The α-ketoglutarate dehydrogenase complex
    (αKGDHC), an enzyme of the tricarboxylic acid cycle, represents a branching point
    controlling glutamate formation and its consumption as a fuel. Hence, modulation
    of the activity of αKGDHC might alter the amount of glutamate available for excitotoxic
    effects. To address this hypothesis, hippocampal neurons in primary co-culture
    with glial cells were exposed to zero-Mg2 buffer to elicit excitotoxicity through
    N-methyl-D-aspartic acid (NMDA) receptor disinhibition. Pretreatment of the cultures
    with succinyl phosphonate, to inhibit αKGDHC, enhanced excitotoxity, whereas promotion
    of αKGDHC activity by pretreatment with thiamine caused an opposite action. Moreover,
    NMDA receptor currents – but not those mediated by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic
    acid (AMPA) receptors – were potentiated in neurons with impaired αKGDHC activity
    and diminished in neurons with boosted αKGDHC activity. The sensitization of NMDA
    receptors involved mGluR1 activation and was accompanied by enhanced neuronal
    discharge activity, elevated basal cytosolic Ca2+ levels, and augmented Ca2+ responses
    evoked by glutamate application. These results suggest that mGluR1-mediated potentiation
    of NMDA receptors contributes to a mechanism by which inhibition of αKGDHC might
    exacerbate glutamate excitotoxicity.
acknowledgement: The technical assistance by Tanja Wagner and Elena Lilliu is gratefully
  acknowledged. This research was funded in whole or in part by the Austrian Science
  Fund (FWF) (P36145 to H.K., PAT8605623 to M.H. and P33799 to A.V.K.]. Open Access
  funding provided by Medical University of Vienna and the Austrian Science Fund (FWF).
  Deposited in PMC for immediate release.
article_number: jcs264420
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Vanessa
  full_name: Goeschl, Vanessa
  last_name: Goeschl
- first_name: Matej
  full_name: Hotka, Matej
  last_name: Hotka
- first_name: Bernhard
  full_name: Hochreiter, Bernhard
  id: e6cab3de-17f6-11ed-9210-c1e42e045e9d
  last_name: Hochreiter
- first_name: Karlheinz
  full_name: Hilber, Karlheinz
  last_name: Hilber
- first_name: Stefan
  full_name: Boehm, Stefan
  last_name: Boehm
- first_name: Andrey V.
  full_name: Kozlov, Andrey V.
  last_name: Kozlov
- first_name: Helmut
  full_name: Kubista, Helmut
  last_name: Kubista
citation:
  ama: Goeschl V, Hotka M, Hochreiter B, et al. α-ketoglutarate dehydrogenase complex
    activity modulates glutamate excitotoxicity via metabotropic regulation of NMDA
    receptors in primary cultures. <i>Journal of Cell Science</i>. 2026;139(8). doi:<a
    href="https://doi.org/10.1242/jcs.264420">10.1242/jcs.264420</a>
  apa: Goeschl, V., Hotka, M., Hochreiter, B., Hilber, K., Boehm, S., Kozlov, A. V.,
    &#38; Kubista, H. (2026). α-ketoglutarate dehydrogenase complex activity modulates
    glutamate excitotoxicity via metabotropic regulation of NMDA receptors in primary
    cultures. <i>Journal of Cell Science</i>. The Company of Biologists. <a href="https://doi.org/10.1242/jcs.264420">https://doi.org/10.1242/jcs.264420</a>
  chicago: Goeschl, Vanessa, Matej Hotka, Bernhard Hochreiter, Karlheinz Hilber, Stefan
    Boehm, Andrey V. Kozlov, and Helmut Kubista. “α-Ketoglutarate Dehydrogenase Complex
    Activity Modulates Glutamate Excitotoxicity via Metabotropic Regulation of NMDA
    Receptors in Primary Cultures.” <i>Journal of Cell Science</i>. The Company of
    Biologists, 2026. <a href="https://doi.org/10.1242/jcs.264420">https://doi.org/10.1242/jcs.264420</a>.
  ieee: V. Goeschl <i>et al.</i>, “α-ketoglutarate dehydrogenase complex activity
    modulates glutamate excitotoxicity via metabotropic regulation of NMDA receptors
    in primary cultures,” <i>Journal of Cell Science</i>, vol. 139, no. 8. The Company
    of Biologists, 2026.
  ista: Goeschl V, Hotka M, Hochreiter B, Hilber K, Boehm S, Kozlov AV, Kubista H.
    2026. α-ketoglutarate dehydrogenase complex activity modulates glutamate excitotoxicity
    via metabotropic regulation of NMDA receptors in primary cultures. Journal of
    Cell Science. 139(8), jcs264420.
  mla: Goeschl, Vanessa, et al. “α-Ketoglutarate Dehydrogenase Complex Activity Modulates
    Glutamate Excitotoxicity via Metabotropic Regulation of NMDA Receptors in Primary
    Cultures.” <i>Journal of Cell Science</i>, vol. 139, no. 8, jcs264420, The Company
    of Biologists, 2026, doi:<a href="https://doi.org/10.1242/jcs.264420">10.1242/jcs.264420</a>.
  short: V. Goeschl, M. Hotka, B. Hochreiter, K. Hilber, S. Boehm, A.V. Kozlov, H.
    Kubista, Journal of Cell Science 139 (2026).
date_created: 2026-05-11T10:52:27Z
date_published: 2026-04-27T00:00:00Z
date_updated: 2026-05-12T06:40:18Z
day: '27'
ddc:
- '570'
department:
- _id: Bio
doi: 10.1242/jcs.264420
external_id:
  pmid:
  - '41834724'
file:
- access_level: open_access
  checksum: 8db35c97588c2f6ef88c7e8d5924cf8c
  content_type: application/pdf
  creator: dernst
  date_created: 2026-05-12T06:27:54Z
  date_updated: 2026-05-12T06:27:54Z
  file_id: '21861'
  file_name: 2026_JourCellScience_Goeschl.pdf
  file_size: 1957057
  relation: main_file
  success: 1
file_date_updated: 2026-05-12T06:27:54Z
has_accepted_license: '1'
intvolume: '       139'
issue: '8'
language:
- iso: eng
month: '04'
oa: 1
oa_version: Published Version
pmid: 1
publication: Journal of Cell Science
publication_identifier:
  eissn:
  - 1477-9137
  issn:
  - 0021-9533
publication_status: published
publisher: The Company of Biologists
quality_controlled: '1'
scopus_import: '1'
status: public
title: α-ketoglutarate dehydrogenase complex activity modulates glutamate excitotoxicity
  via metabotropic regulation of NMDA receptors in primary cultures
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: 139
year: '2026'
...
---
OA_type: closed access
_id: '20870'
abstract:
- lang: eng
  text: RNA sequencing (RNA-seq) methodologies have evolved rapidly, offering powerful
    tools to study gene expression, transcriptome dynamics, and molecular mechanisms
    in various biological contexts. However, the complexity of these approaches poses
    challenges in data interpretation, sensitivity, and applicability. This chapter
    provides a comprehensive overview of RNA-seq methodologies, highlighting their
    advantages, limitations, and applications, particularly in cardiovascular research.
    Bulk RNA sequencing enables high-throughput gene expression profiling but lacks
    the resolution to capture cellular heterogeneity and spatial context. Direct RNA
    sequencing preserves native RNA modifications, offering insights into post-transcriptional
    regulation, though it remains technically challenging. Single-cell RNA sequencing
    (scRNA-seq) and spatial transcriptomics (ST) bridge these gaps by resolving transcriptomic
    complexity at the cellular level and within tissue architecture, providing crucial
    insights into disease mechanisms such as atherosclerosis. By summarizing the strengths
    and limitations of these methodologies, this chapter aims to guide researchers
    in selecting the most suitable transcriptomic approach for their studies, ultimately
    advancing precision medicine and biomarker discovery in cardiovascular disease.
article_processing_charge: No
author:
- first_name: Victoria
  full_name: Stopa, Victoria
  last_name: Stopa
- first_name: Miron
  full_name: Sopić, Miron
  last_name: Sopić
- first_name: Guanliang
  full_name: Li, Guanliang
  last_name: Li
- first_name: Judith
  full_name: Sluimer, Judith
  last_name: Sluimer
- first_name: José
  full_name: Basílio, José
  last_name: Basílio
- first_name: Sander W.
  full_name: van der Laan, Sander W.
  last_name: van der Laan
- first_name: David P.
  full_name: Kreil, David P.
  last_name: Kreil
- first_name: Yvan
  full_name: Devaux, Yvan
  last_name: Devaux
- first_name: Bernhard
  full_name: Hochreiter, Bernhard
  id: e6cab3de-17f6-11ed-9210-c1e42e045e9d
  last_name: Hochreiter
citation:
  ama: 'Stopa V, Sopić M, Li G, et al. Essentials of transcriptomic methods: Navigating
    through RNA sequencing and beyond. In: Devaux Y, Sopic M, eds. <i>Transcriptomics
    in Atherosclerosis</i>. Elsevier; 2025:131-172. doi:<a href="https://doi.org/10.1016/b978-0-443-33064-3.00016-5">10.1016/b978-0-443-33064-3.00016-5</a>'
  apa: 'Stopa, V., Sopić, M., Li, G., Sluimer, J., Basílio, J., van der Laan, S. W.,
    … Hochreiter, B. (2025). Essentials of transcriptomic methods: Navigating through
    RNA sequencing and beyond. In Y. Devaux &#38; M. Sopic (Eds.), <i>Transcriptomics
    in Atherosclerosis</i> (pp. 131–172). Elsevier. <a href="https://doi.org/10.1016/b978-0-443-33064-3.00016-5">https://doi.org/10.1016/b978-0-443-33064-3.00016-5</a>'
  chicago: 'Stopa, Victoria, Miron Sopić, Guanliang Li, Judith Sluimer, José Basílio,
    Sander W. van der Laan, David P. Kreil, Yvan Devaux, and Bernhard Hochreiter.
    “Essentials of Transcriptomic Methods: Navigating through RNA Sequencing and Beyond.”
    In <i>Transcriptomics in Atherosclerosis</i>, edited by Yvan Devaux and Miron
    Sopic, 131–72. Elsevier, 2025. <a href="https://doi.org/10.1016/b978-0-443-33064-3.00016-5">https://doi.org/10.1016/b978-0-443-33064-3.00016-5</a>.'
  ieee: 'V. Stopa <i>et al.</i>, “Essentials of transcriptomic methods: Navigating
    through RNA sequencing and beyond,” in <i>Transcriptomics in Atherosclerosis</i>,
    Y. Devaux and M. Sopic, Eds. Elsevier, 2025, pp. 131–172.'
  ista: 'Stopa V, Sopić M, Li G, Sluimer J, Basílio J, van der Laan SW, Kreil DP,
    Devaux Y, Hochreiter B. 2025.Essentials of transcriptomic methods: Navigating
    through RNA sequencing and beyond. In: Transcriptomics in Atherosclerosis. , 131–172.'
  mla: 'Stopa, Victoria, et al. “Essentials of Transcriptomic Methods: Navigating
    through RNA Sequencing and Beyond.” <i>Transcriptomics in Atherosclerosis</i>,
    edited by Yvan Devaux and Miron Sopic, Elsevier, 2025, pp. 131–72, doi:<a href="https://doi.org/10.1016/b978-0-443-33064-3.00016-5">10.1016/b978-0-443-33064-3.00016-5</a>.'
  short: V. Stopa, M. Sopić, G. Li, J. Sluimer, J. Basílio, S.W. van der Laan, D.P.
    Kreil, Y. Devaux, B. Hochreiter, in:, Y. Devaux, M. Sopic (Eds.), Transcriptomics
    in Atherosclerosis, Elsevier, 2025, pp. 131–172.
date_created: 2025-12-29T12:16:22Z
date_published: 2025-10-24T00:00:00Z
date_updated: 2026-01-05T11:49:54Z
day: '24'
department:
- _id: Bio
doi: 10.1016/b978-0-443-33064-3.00016-5
editor:
- first_name: Yvan
  full_name: Devaux, Yvan
  last_name: Devaux
- first_name: Miron
  full_name: Sopic, Miron
  last_name: Sopic
language:
- iso: eng
month: '10'
oa_version: None
page: 131-172
publication: Transcriptomics in Atherosclerosis
publication_identifier:
  isbn:
  - '9780443330643'
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: 'Essentials of transcriptomic methods: Navigating through RNA sequencing and
  beyond'
type: book_chapter
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2025'
...