Abstract
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.
| Original language | English |
|---|---|
| Article number | 17747 |
| Journal | Scientific Reports |
| Volume | 11 |
| Issue number | 1 |
| ISSN | 2045-2322 |
| DOIs | |
| Publication status | Published - 12.2021 |
Funding
This work was supported by the Grant of Ministry of Education, Science and Technological Development of the Republic of Serbia (451-03-9/2021-14/ 200017) to I.P and D.F, Grant from the Deutsche Forschungsgemeinschaft (GA 427/12-1) to P.G and by grants from the Deutsche Forschungsgemeinschaft (DFG) IN 68/3-1, the Ingeborg Ständer Foundation, the ERA-NET NEURON program, the Bundesministerium für Bildung und Forschung (BMBF) under the frame of Neuron Cofund (ERA-NET NEURONNMDAR-PSY) and the Swiss National Foundation (SNF) 186346 to D.I. We gratefully thank the staff from Faculty of Medicine, University of Belgrade for using Chemidoc-MP System (Bio-Rad).
