The atypical antidepressant tianeptine confers neuroprotection against oxygen-glucose deprivation

被引:1
作者
Ersoy, Burcu [1 ,2 ,3 ,4 ,5 ]
Herzog, Marie-Louise [1 ,2 ,3 ,4 ,6 ]
Pan, Wen [1 ,2 ,3 ,4 ,6 ]
Schilling, Simone [1 ,2 ,3 ,4 ,6 ,7 ]
Endres, Matthias [1 ,2 ,3 ,4 ,6 ,8 ,9 ,10 ]
Goettert, Ria [1 ,2 ,3 ,4 ,6 ]
Kronenberg, Golo D. [11 ]
Gertz, Karen [1 ,2 ,3 ,4 ,6 ,8 ]
机构
[1] Charite Univ Med Berlin, Dept Neurol, Berlin, Germany
[2] Free Univ Berlin, Berlin, Germany
[3] Humboldt Univ, Berlin, Germany
[4] Charite Univ Med Berlin, Ctr Stroke Res Berlin, Dept Expt Neurol, Berlin, Germany
[5] Charite Univ Med Berlin, Berlin Brandenburg Sch Regenerat Therapies, Berlin, Germany
[6] DZHK German Ctr Cardiovasc Res, Partner Site, Berlin, Germany
[7] Univ Med Berlin, Berlin Inst Hlth Charite, Berlin, Germany
[8] Charite Univ Med Berlin, Einstein Ctr Neurosci, Berlin, Germany
[9] DZNE German Ctr Neurodegenerat Dis, Partner Site, Berlin, Germany
[10] DZPG German Ctr Mental Hlth, Partner Site, Berlin, Germany
[11] Univ Hosp Psychiat Zurich, Dept Psychiat Psychotherapy & Psychosomat, Lenggstr 31,POB 363, CH-8032 Zurich, Switzerland
关键词
Tianeptine; Ischemia; Stroke; Neuroprotection; Serotonin; TRANSIENT FOREBRAIN ISCHEMIA; NEURONAL CELL-DEATH; POSTISCHEMIC BRAIN; SIGNALING PATHWAY; REDUCES APOPTOSIS; OXIDATIVE STRESS; GENE LISTS; IN-VIVO; GLUTAMATE; RECEPTOR;
D O I
10.1007/s00406-023-01685-9
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
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 & mu;M) significantly enhanced neuron viability as measured by MTT assay and reduced cell death and LDH release. CIT (10 & mu;M) and FLU (1 & mu;M) 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 & mu;M) 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.
引用
收藏
页码:777 / 791
页数:15
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