Down-regulation of habenular calcium-dependent secretion activator 2 induces despair-like behavior

Abstract Calcium-dependent secretion activator 2 (CAPS2) regulates the trafficking and exocytosis of neuropeptide-containing dense-core vesicles (DCVs). CAPS2 is prominently expressed in the medial habenula (MHb), which is related to depressive behavior; however, how MHb neurons cause depressive sym...

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Autores principales:	Hyeijung Yoo, Soo Hyun Yang, Jin Yong Kim, Esther Yang, Hyung Sun Park, Se Jeong Lee, Im Joo Rhyu, Gustavo Turecki, Hyun Woo Lee, Hyun Kim
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/194c68099bbb42b489f1a57dfe753a47
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spelling	oai:doaj.org-article:194c68099bbb42b489f1a57dfe753a472021-12-02T12:15:02ZDown-regulation of habenular calcium-dependent secretion activator 2 induces despair-like behavior10.1038/s41598-021-83310-02045-2322https://doaj.org/article/194c68099bbb42b489f1a57dfe753a472021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-83310-0https://doaj.org/toc/2045-2322Abstract Calcium-dependent secretion activator 2 (CAPS2) regulates the trafficking and exocytosis of neuropeptide-containing dense-core vesicles (DCVs). CAPS2 is prominently expressed in the medial habenula (MHb), which is related to depressive behavior; however, how MHb neurons cause depressive symptoms and the role of CAPS2 remains unclear. We hypothesized that dysfunction of MHb CAPS neurons might cause defects in neuropeptide secretion and the activity of monoaminergic centers, resulting in depressive-like behaviors. In this study, we examined (1) CAPS2 expression in the habenula of depression animal models and major depressive disorder patients and (2) the effects of down-regulation of MHb CAPS2 on the animal behaviors, synaptic transmission in the interpeduncular nucleus (IPN), and neuronal activity of monoamine centers. Habenular CAPS2 expression was decreased in the rat chronic restraint stress model, mouse learned helplessness model, and showed tendency to decrease in depression patients who died by suicide. Knockdown of CAPS2 in the mouse habenula evoked despair-like behavior and a reduction of the release of DCVs in the IPN. Neuronal activity of IPN and monoaminergic centers was also reduced. These results implicate MHb CAPS2 as playing a pivotal role in depressive behavior through the regulation of neuropeptide secretion of the MHb-IPN pathway and the activity of monoaminergic centers.Hyeijung YooSoo Hyun YangJin Yong KimEsther YangHyung Sun ParkSe Jeong LeeIm Joo RhyuGustavo TureckiHyun Woo LeeHyun KimNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hyeijung Yoo Soo Hyun Yang Jin Yong Kim Esther Yang Hyung Sun Park Se Jeong Lee Im Joo Rhyu Gustavo Turecki Hyun Woo Lee Hyun Kim Down-regulation of habenular calcium-dependent secretion activator 2 induces despair-like behavior
description	Abstract Calcium-dependent secretion activator 2 (CAPS2) regulates the trafficking and exocytosis of neuropeptide-containing dense-core vesicles (DCVs). CAPS2 is prominently expressed in the medial habenula (MHb), which is related to depressive behavior; however, how MHb neurons cause depressive symptoms and the role of CAPS2 remains unclear. We hypothesized that dysfunction of MHb CAPS neurons might cause defects in neuropeptide secretion and the activity of monoaminergic centers, resulting in depressive-like behaviors. In this study, we examined (1) CAPS2 expression in the habenula of depression animal models and major depressive disorder patients and (2) the effects of down-regulation of MHb CAPS2 on the animal behaviors, synaptic transmission in the interpeduncular nucleus (IPN), and neuronal activity of monoamine centers. Habenular CAPS2 expression was decreased in the rat chronic restraint stress model, mouse learned helplessness model, and showed tendency to decrease in depression patients who died by suicide. Knockdown of CAPS2 in the mouse habenula evoked despair-like behavior and a reduction of the release of DCVs in the IPN. Neuronal activity of IPN and monoaminergic centers was also reduced. These results implicate MHb CAPS2 as playing a pivotal role in depressive behavior through the regulation of neuropeptide secretion of the MHb-IPN pathway and the activity of monoaminergic centers.
format	article
author	Hyeijung Yoo Soo Hyun Yang Jin Yong Kim Esther Yang Hyung Sun Park Se Jeong Lee Im Joo Rhyu Gustavo Turecki Hyun Woo Lee Hyun Kim
author_facet	Hyeijung Yoo Soo Hyun Yang Jin Yong Kim Esther Yang Hyung Sun Park Se Jeong Lee Im Joo Rhyu Gustavo Turecki Hyun Woo Lee Hyun Kim
author_sort	Hyeijung Yoo
title	Down-regulation of habenular calcium-dependent secretion activator 2 induces despair-like behavior
title_short	Down-regulation of habenular calcium-dependent secretion activator 2 induces despair-like behavior
title_full	Down-regulation of habenular calcium-dependent secretion activator 2 induces despair-like behavior
title_fullStr	Down-regulation of habenular calcium-dependent secretion activator 2 induces despair-like behavior
title_full_unstemmed	Down-regulation of habenular calcium-dependent secretion activator 2 induces despair-like behavior
title_sort	down-regulation of habenular calcium-dependent secretion activator 2 induces despair-like behavior
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/194c68099bbb42b489f1a57dfe753a47
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Down-regulation of habenular calcium-dependent secretion activator 2 induces despair-like behavior

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