Journal Article

DZNE-2024-00611

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png The atypical antidepressant tianeptine confers neuroprotection against oxygen-glucose deprivation.

Ersoy, B. ; Herzog, M.-L. ; Pan, W. ; Schilling, S. ; Endres, M.DZNE* ; Göttert, R. ; Kronenberg, G. D. ; Gertz, K.

2024
Springer Heidelberg

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Please use a persistent id in citations: doi:10.1007/s00406-023-01685-9

Abstract: 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 μM) significantly enhanced neuron viability as measured by MTT assay and reduced cell death and LDH release. CIT (10 μM) and FLU (1 μM) 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 μM) 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.

Keyword(s): Animals (MeSH) ; Mice (MeSH) ; Glucose: deficiency (MeSH) ; Neuroprotective Agents: pharmacology (MeSH) ; Neurons: drug effects (MeSH) ; Neurons: metabolism (MeSH) ; Thiazepines: pharmacology (MeSH) ; Cells, Cultured (MeSH) ; Cerebral Cortex: drug effects (MeSH) ; Cerebral Cortex: metabolism (MeSH) ; Citalopram: pharmacology (MeSH) ; Fluoxetine: pharmacology (MeSH) ; Serotonin: metabolism (MeSH) ; Mice, Inbred C57BL (MeSH) ; Cell Hypoxia: drug effects (MeSH) ; Cell Hypoxia: physiology (MeSH) ; Oxygen (MeSH) ; Antidepressive Agents, Tricyclic: pharmacology (MeSH) ; Ischemia ; Neuroprotection ; Serotonin ; Stroke ; Tianeptine ; tianeptine ; Glucose ; Neuroprotective Agents ; Thiazepines ; Citalopram ; Fluoxetine ; Serotonin ; Oxygen ; Antidepressive Agents, Tricyclic

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Contributing Institute(s):

1. Interdisciplinary Dementia Research (AG Endres)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2024

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Database coverage:
; ; ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; DEAL Springer ; Ebsco Academic Search ; Essential Science Indicators ; IF < 5 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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