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.
Highlights
Deregulation of synaptic function and neurotransmission has been linked with the development of major depression disorder (MDD)
The alterations in neurotransmission processes mediated via serotonin, dopamine and gamma-aminobutyric acid (GABA), as well as the reduction in synapse number and their functionality have been associated with MDD
Many molecular alterations associated with the pathophysiology and severity of MDD as well as the effects of the fast acting antidepressants reside within the s ynapse[47,48]
Summary
Deregulation of synaptic function and neurotransmission has been linked with the development of major depression disorder (MDD). Our overall findings revealed that synaptic vesicle dynamics, 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 stressrelated mood disorders. Acting as a positive allosteric modulator of the α-amino-3-hydroxy-5-methy-l-4isoxazole propionate (AMPA)-type glutamate receptor (AMPAkine), Tian prolongs and strengthens synaptic transmission[31] It is considered as one of the nootropics for improving cognitive performances in healthy individuals within h ours[32]. We performed a comparative proteomics with synapse membrane-enriched (synaptosome) hippocampal fractions of adult male Wistar rats exposed to CSIS (6 weeks) and after chronic Tian treatment of controls (3 weeks) and CSIS-exposed rats (lasting 3 weeks of 6-week-CSIS). The results of this study may be helpful in identification of deregulated pathways involved in M D33 and highlight possible routes of Tian’s nootropic and antidepressant activity
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
