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

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 ac...

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Autores principales:	Ivana Perić, Victor Costina, Snežana Djordjević, Peter Gass, Peter Findeisen, Dragoš Inta, Stefan Borgwardt, Dragana Filipović
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/71e0fdfc3cc54c37a78301bc7c80d617
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spelling	oai:doaj.org-article:71e0fdfc3cc54c37a78301bc7c80d6172021-12-02T17:19:17ZTianeptine modulates synaptic vesicle dynamics and favors synaptic mitochondria processes in socially isolated rats10.1038/s41598-021-97186-72045-2322https://doaj.org/article/71e0fdfc3cc54c37a78301bc7c80d6172021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-97186-7https://doaj.org/toc/2045-2322Abstract 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.Ivana PerićVictor CostinaSnežana DjordjevićPeter GassPeter FindeisenDragoš IntaStefan BorgwardtDragana FilipovićNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ivana Perić Victor Costina Snežana Djordjević Peter Gass Peter Findeisen Dragoš Inta Stefan Borgwardt Dragana Filipović Tianeptine modulates synaptic vesicle dynamics and favors synaptic mitochondria processes in socially isolated rats
description	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.
format	article
author	Ivana Perić Victor Costina Snežana Djordjević Peter Gass Peter Findeisen Dragoš Inta Stefan Borgwardt Dragana Filipović
author_facet	Ivana Perić Victor Costina Snežana Djordjević Peter Gass Peter Findeisen Dragoš Inta Stefan Borgwardt Dragana Filipović
author_sort	Ivana Perić
title	Tianeptine modulates synaptic vesicle dynamics and favors synaptic mitochondria processes in socially isolated rats
title_short	Tianeptine modulates synaptic vesicle dynamics and favors synaptic mitochondria processes in socially isolated rats
title_full	Tianeptine modulates synaptic vesicle dynamics and favors synaptic mitochondria processes in socially isolated rats
title_fullStr	Tianeptine modulates synaptic vesicle dynamics and favors synaptic mitochondria processes in socially isolated rats
title_full_unstemmed	Tianeptine modulates synaptic vesicle dynamics and favors synaptic mitochondria processes in socially isolated rats
title_sort	tianeptine modulates synaptic vesicle dynamics and favors synaptic mitochondria processes in socially isolated rats
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/71e0fdfc3cc54c37a78301bc7c80d617
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Tianeptine modulates synaptic vesicle dynamics and favors synaptic mitochondria processes in socially isolated rats

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