PMID- 37653354 OWN - NLM STAT- Publisher LR - 20230831 IS - 1433-8491 (Electronic) IS - 0940-1334 (Linking) DP - 2023 Sep 1 TI - The atypical antidepressant tianeptine confers neuroprotection against oxygen-glucose deprivation. LID - 10.1007/s00406-023-01685-9 [doi] AB - Proregenerative and neuroprotective effects of antidepressants are an important topic of inquiry in neuropsychiatric research. Oxygen-glucose deprivation (OGD) mimics key aspects of ischemic injury in vitro. Here, we studied the effects of 24-h pretreatment with serotonin (5-HT), citalopram (CIT), fluoxetine (FLU), and tianeptine (TIA) on primary mouse cortical neurons subjected to transient OGD. 5-HT (50 muM) significantly enhanced neuron viability as measured by MTT assay and reduced cell death and LDH release. CIT (10 muM) and FLU (1 muM) did not increase the effects of 5-HT and neither antidepressant conferred neuroprotection in the absence of supplemental 5-HT in serum-free cell culture medium. By contrast, pre-treatment with TIA (10 muM) resulted in robust neuroprotection, even in the absence of 5-HT. Furthermore, TIA inhibited mRNA transcription of candidate genes related to cell death and hypoxia and attenuated lipid peroxidation, a hallmark of neuronal injury. Finally, deep RNA sequencing of primary neurons subjected to OGD demonstrated that OGD induces many pathways relating to cell survival, the inflammation-immune response, synaptic dysregulation and apoptosis, and that TIA pretreatment counteracted these effects of OGD. In conclusion, this study highlights the comparative strength of the 5-HT independent neuroprotective effects of TIA and identifies the molecular pathways involved. CI - (c) 2023. The Author(s). FAU - Ersoy, Burcu AU - Ersoy B AD - Department of Neurology, Charite-Universitatsmedizin Berlin, Corporate Member of Freie Universitat Berlin and Humboldt-Universitat zu Berlin, Berlin, Germany. AD - Center for Stroke Research Berlin, Department of Experimental Neurology, Charite-Universitatsmedizin Berlin, Corporate member of Freie Universitat Berlin and Humboldt-Universitat zu Berlin, Berlin, Germany. AD - Berlin-Brandenburg School for Regenerative Therapies, Charite-Universitatsmedizin Berlin, Berlin, Germany. FAU - Herzog, Marie-Louise AU - Herzog ML AD - Department of Neurology, Charite-Universitatsmedizin Berlin, Corporate Member of Freie Universitat Berlin and Humboldt-Universitat zu Berlin, Berlin, Germany. AD - Center for Stroke Research Berlin, Department of Experimental Neurology, Charite-Universitatsmedizin Berlin, Corporate member of Freie Universitat Berlin and Humboldt-Universitat zu Berlin, Berlin, Germany. AD - DZHK (German Center for Cardiovascular Research), Partner site, Berlin, Germany. FAU - Pan, Wen AU - Pan W AD - Department of Neurology, Charite-Universitatsmedizin Berlin, Corporate Member of Freie Universitat Berlin and Humboldt-Universitat zu Berlin, Berlin, Germany. AD - Center for Stroke Research Berlin, Department of Experimental Neurology, Charite-Universitatsmedizin Berlin, Corporate member of Freie Universitat Berlin and Humboldt-Universitat zu Berlin, Berlin, Germany. AD - DZHK (German Center for Cardiovascular Research), Partner site, Berlin, Germany. FAU - Schilling, Simone AU - Schilling S AD - Department of Neurology, Charite-Universitatsmedizin Berlin, Corporate Member of Freie Universitat Berlin and Humboldt-Universitat zu Berlin, Berlin, Germany. AD - Center for Stroke Research Berlin, Department of Experimental Neurology, Charite-Universitatsmedizin Berlin, Corporate member of Freie Universitat Berlin and Humboldt-Universitat zu Berlin, Berlin, Germany. AD - DZHK (German Center for Cardiovascular Research), Partner site, Berlin, Germany. AD - Berlin Institute of Health at Charite, Universitatsmedizin Berlin, Berlin, Germany. FAU - Endres, Matthias AU - Endres M AD - Department of Neurology, Charite-Universitatsmedizin Berlin, Corporate Member of Freie Universitat Berlin and Humboldt-Universitat zu Berlin, Berlin, Germany. AD - Center for Stroke Research Berlin, Department of Experimental Neurology, Charite-Universitatsmedizin Berlin, Corporate member of Freie Universitat Berlin and Humboldt-Universitat zu Berlin, Berlin, Germany. AD - DZHK (German Center for Cardiovascular Research), Partner site, Berlin, Germany. AD - Einstein Center for Neurosciences, Charite-Universitatsmedizin Berlin, Berlin, Germany. AD - DZNE (German Center for Neurodegenerative Diseases), Partner site, Berlin, Germany. AD - DZPG (German Center for Mental Health), Partner site, Berlin, Germany. FAU - Gottert, Ria AU - Gottert R AD - Department of Neurology, Charite-Universitatsmedizin Berlin, Corporate Member of Freie Universitat Berlin and Humboldt-Universitat zu Berlin, Berlin, Germany. AD - Center for Stroke Research Berlin, Department of Experimental Neurology, Charite-Universitatsmedizin Berlin, Corporate member of Freie Universitat Berlin and Humboldt-Universitat zu Berlin, Berlin, Germany. AD - DZHK (German Center for Cardiovascular Research), Partner site, Berlin, Germany. FAU - Kronenberg, Golo D AU - Kronenberg GD AD - Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital of Psychiatry Zurich, Lenggstrasse 31, P.O. Box 363, 8032, Zurich, Switzerland. FAU - Gertz, Karen AU - Gertz K AUID- ORCID: 0000-0002-1203-641X AD - Department of Neurology, Charite-Universitatsmedizin Berlin, Corporate Member of Freie Universitat Berlin and Humboldt-Universitat zu Berlin, Berlin, Germany. karen.gertz@charite.de. AD - Center for Stroke Research Berlin, Department of Experimental Neurology, Charite-Universitatsmedizin Berlin, Corporate member of Freie Universitat Berlin and Humboldt-Universitat zu Berlin, Berlin, Germany. karen.gertz@charite.de. AD - DZHK (German Center for Cardiovascular Research), Partner site, Berlin, Germany. karen.gertz@charite.de. AD - Einstein Center for Neurosciences, Charite-Universitatsmedizin Berlin, Berlin, Germany. karen.gertz@charite.de. LA - eng GR - EXC-2049 - 390688087/Deutsche Forschungsgemeinschaft/ GR - ReTune TRR 295- 424778381/Deutsche Forschungsgemeinschaft/ GR - KR 2956/4-1/Deutsche Forschungsgemeinschaft/ GR - GE 2576/3-1/Deutsche Forschungsgemeinschaft/ PT - Journal Article DEP - 20230901 PL - Germany TA - Eur Arch Psychiatry Clin Neurosci JT - European archives of psychiatry and clinical neuroscience JID - 9103030 SB - IM OTO - NOTNLM OT - Ischemia OT - Neuroprotection OT - Serotonin OT - Stroke OT - Tianeptine EDAT- 2023/09/01 00:41 MHDA- 2023/09/01 00:41 CRDT- 2023/08/31 23:42 PHST- 2023/06/17 00:00 [received] PHST- 2023/08/14 00:00 [accepted] PHST- 2023/09/01 00:41 [medline] PHST- 2023/09/01 00:41 [pubmed] PHST- 2023/08/31 23:42 [entrez] AID - 10.1007/s00406-023-01685-9 [pii] AID - 10.1007/s00406-023-01685-9 [doi] PST - aheadofprint SO - Eur Arch Psychiatry Clin Neurosci. 2023 Sep 1. doi: 10.1007/s00406-023-01685-9.