Tianeptine modulates synaptic vesicle dynamics and favors synaptic mitochondria processes in socially isolated rats

Deregulation of synaptic function and neurotransmission has been linked with the development of major depression disorder (MDD). Tianeptine (Tian) has been used as antidepressant with anxiolytic properties and recently as a nootropic to improve cognitive performance, but its mechanism of action is u...

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Main Authors: Peric, Ivana (Author) , Costina, Victor (Author) , Djordjević, Snežana (Author) , Gass, Peter (Author) , Findeisen, Peter (Author) , Inta, Dragos (Author) , Borgwardt, Stefan (Author) , Filipović, Dragana (Author)
Format: Article (Journal)
Language:English
Published: 07 September 2021
In: Scientific reports
Year: 2021, Volume: 11, Pages: 1-15
ISSN:2045-2322
DOI:10.1038/s41598-021-97186-7
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/s41598-021-97186-7
Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/s41598-021-97186-7
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Author Notes:Ivana Perić, Victor Costina, Snežana Djordjević, Peter Gass, Peter Findeisen, Dragoš Inta, Stefan Borgwardt and Dragana Filipović
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Summary:Deregulation of synaptic function and neurotransmission has been linked with the development of major depression disorder (MDD). Tianeptine (Tian) has been used as antidepressant with anxiolytic properties and recently as a nootropic to improve cognitive performance, but its mechanism of action is unknown. We conducted a proteomic study on the hippocampal synaptosomal fractions of adult male Wistar rats exposed to chronic social isolation (CSIS, 6 weeks), an animal model of depression and after chronic Tian treatment in controls (nootropic effect) and CSIS-exposed rats (lasting 3 weeks of 6-week CSIS) (therapeutic effect). Increased expression of Syn1 and Camk2-related neurotransmission, vesicle transport and energy processes in Tian-treated controls were found. CSIS led to upregulation of proteins associated with actin cytoskeleton, signaling transduction and glucose metabolism. In CSIS rats, Tian up-regulated proteins involved in mitochondrial energy production, mitochondrial transport and dynamics, antioxidative defense and glutamate clearance, while attenuating the CSIS-increased glycolytic pathway and cytoskeleton organization proteins expression and decreased the expression of proteins involved in V-ATPase and vesicle endocytosis. Our overall findings revealed that synaptic vesicle dynamics, specifically exocytosis, and mitochondria-related energy processes might be key biological pathways modulated by the effective nootropic and antidepressant treatment with Tian and be a potential target for therapeutic efficacy of the stress-related mood disorders.
Item Description:Gesehen am 02.02.2023
Physical Description:Online Resource
ISSN:2045-2322
DOI:10.1038/s41598-021-97186-7