[{"month":"04","date_published":"2026-04-27T00:00:00Z","author":[{"full_name":"Goeschl, Vanessa","first_name":"Vanessa","last_name":"Goeschl"},{"full_name":"Hotka, Matej","last_name":"Hotka","first_name":"Matej"},{"full_name":"Hochreiter, Bernhard","id":"e6cab3de-17f6-11ed-9210-c1e42e045e9d","last_name":"Hochreiter","first_name":"Bernhard"},{"full_name":"Hilber, Karlheinz","first_name":"Karlheinz","last_name":"Hilber"},{"full_name":"Boehm, Stefan","first_name":"Stefan","last_name":"Boehm"},{"first_name":"Andrey V.","last_name":"Kozlov","full_name":"Kozlov, Andrey V."},{"last_name":"Kubista","first_name":"Helmut","full_name":"Kubista, Helmut"}],"type":"journal_article","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","article_type":"original","status":"public","intvolume":"       139","department":[{"_id":"Bio"}],"date_updated":"2026-05-12T06:40:18Z","oa":1,"publisher":"The Company of Biologists","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."}],"external_id":{"pmid":["41834724"]},"oa_version":"Published Version","_id":"21860","scopus_import":"1","has_accepted_license":"1","quality_controlled":"1","pmid":1,"license":"https://creativecommons.org/licenses/by/4.0/","doi":"10.1242/jcs.264420","issue":"8","PlanS_conform":"1","citation":{"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>.","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>.","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>","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.","short":"V. Goeschl, M. Hotka, B. Hochreiter, K. Hilber, S. Boehm, A.V. Kozlov, H. Kubista, Journal of Cell Science 139 (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.","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>"},"file_date_updated":"2026-05-12T06:27:54Z","OA_place":"publisher","volume":139,"publication_identifier":{"eissn":["1477-9137"],"issn":["0021-9533"]},"year":"2026","day":"27","article_number":"jcs264420","ddc":["570"],"date_created":"2026-05-11T10:52:27Z","language":[{"iso":"eng"}],"tmp":{"image":"/images/cc_by.png","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"OA_type":"hybrid","file":[{"content_type":"application/pdf","success":1,"file_id":"21861","access_level":"open_access","date_created":"2026-05-12T06:27:54Z","date_updated":"2026-05-12T06:27:54Z","file_size":1957057,"relation":"main_file","file_name":"2026_JourCellScience_Goeschl.pdf","creator":"dernst","checksum":"8db35c97588c2f6ef88c7e8d5924cf8c"}],"publication":"Journal of Cell Science","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.","title":"α-ketoglutarate dehydrogenase complex activity modulates glutamate excitotoxicity via metabotropic regulation of NMDA receptors in primary cultures","article_processing_charge":"Yes (via OA deal)","publication_status":"published"},{"scopus_import":"1","_id":"20870","oa_version":"None","page":"131-172","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."}],"publisher":"Elsevier","citation":{"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>.","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>.","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>","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.","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.","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>"},"publication_status":"published","doi":"10.1016/b978-0-443-33064-3.00016-5","article_processing_charge":"No","title":"Essentials of transcriptomic methods: Navigating through RNA sequencing and beyond","publication":"Transcriptomics in Atherosclerosis","editor":[{"full_name":"Devaux, Yvan","first_name":"Yvan","last_name":"Devaux"},{"full_name":"Sopic, Miron","last_name":"Sopic","first_name":"Miron"}],"quality_controlled":"1","status":"public","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","type":"book_chapter","day":"24","year":"2025","publication_identifier":{"isbn":["9780443330643"]},"author":[{"last_name":"Stopa","first_name":"Victoria","full_name":"Stopa, Victoria"},{"full_name":"Sopić, Miron","last_name":"Sopić","first_name":"Miron"},{"full_name":"Li, Guanliang","first_name":"Guanliang","last_name":"Li"},{"last_name":"Sluimer","first_name":"Judith","full_name":"Sluimer, Judith"},{"full_name":"Basílio, José","first_name":"José","last_name":"Basílio"},{"last_name":"van der Laan","first_name":"Sander W.","full_name":"van der Laan, Sander W."},{"first_name":"David P.","last_name":"Kreil","full_name":"Kreil, David P."},{"last_name":"Devaux","first_name":"Yvan","full_name":"Devaux, Yvan"},{"last_name":"Hochreiter","first_name":"Bernhard","full_name":"Hochreiter, Bernhard","id":"e6cab3de-17f6-11ed-9210-c1e42e045e9d"}],"month":"10","date_published":"2025-10-24T00:00:00Z","OA_type":"closed access","language":[{"iso":"eng"}],"date_updated":"2026-01-05T11:49:54Z","department":[{"_id":"Bio"}],"date_created":"2025-12-29T12:16:22Z"}]