Down-regulation of cholinergic signaling in the habenula induces anhedonia-like behavior

Abstract Dysfunction of cholinergic signaling in the brain has long been believed to be associated with depressive disorders. However, the functional impact of habenular cholinergic signaling on the specified depressive behaviors is not well understood. Here, we demonstrated that the expression leve...

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Autores principales:	Seungrie Han, Soo Hyun Yang, Jin Yong Kim, Seojung Mo, Esther Yang, Ki Myung Song, Byung-Joo Ham, Naguib Mechawar, Gustavo Turecki, Hyun Woo Lee, Hyun Kim
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9e4e5fd4bdd14140afe8b403873d4cdf
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spelling	oai:doaj.org-article:9e4e5fd4bdd14140afe8b403873d4cdf2021-12-02T12:30:44ZDown-regulation of cholinergic signaling in the habenula induces anhedonia-like behavior10.1038/s41598-017-01088-62045-2322https://doaj.org/article/9e4e5fd4bdd14140afe8b403873d4cdf2017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01088-6https://doaj.org/toc/2045-2322Abstract Dysfunction of cholinergic signaling in the brain has long been believed to be associated with depressive disorders. However, the functional impact of habenular cholinergic signaling on the specified depressive behaviors is not well understood. Here, we demonstrated that the expression levels of cholinergic signaling genes (CHAT, VACHT, CHT, CHRNA3, CHRNB3 and CHRNB4) were down-regulated in a chronic restraint stress (CRS) rat model of depression, in which rats display depression-like behaviors such as anhedonia and mood despair. Moreover, knockdown of CHAT in the rat habenula was sufficient to evoke anhedonia-like behavior. The anhedonia-like behavior induced by CHAT knockdown was not reversed by chronic administration of the selective serotonin reuptake inhibitor fluoxetine. To determine whether habenular cholinergic signaling is associated with regulation of dopamine neurons in the ventral tegmental area (VTA) and serotonin neurons in the dorsal raphe nucleus (DRN), we used CHAT::cre transgenic mice expressing the Designer Receptors Exclusively Activated by Designer Drugs (DREADD). Pharmacogenetic activation of habenular cholinergic neurons induces the excitation of dopamine neurons in the VTA and reduces the immunoreactivity of 5-hydroxytryptamine (5-HT) in the DRN. Habenular cholinergic gene down-regulation was recapitulated in the postmortem habenula of suicide victims diagnosed with major depressive disorder (MDD).Seungrie HanSoo Hyun YangJin Yong KimSeojung MoEsther YangKi Myung SongByung-Joo HamNaguib MechawarGustavo TureckiHyun Woo LeeHyun KimNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Seungrie Han Soo Hyun Yang Jin Yong Kim Seojung Mo Esther Yang Ki Myung Song Byung-Joo Ham Naguib Mechawar Gustavo Turecki Hyun Woo Lee Hyun Kim Down-regulation of cholinergic signaling in the habenula induces anhedonia-like behavior
description	Abstract Dysfunction of cholinergic signaling in the brain has long been believed to be associated with depressive disorders. However, the functional impact of habenular cholinergic signaling on the specified depressive behaviors is not well understood. Here, we demonstrated that the expression levels of cholinergic signaling genes (CHAT, VACHT, CHT, CHRNA3, CHRNB3 and CHRNB4) were down-regulated in a chronic restraint stress (CRS) rat model of depression, in which rats display depression-like behaviors such as anhedonia and mood despair. Moreover, knockdown of CHAT in the rat habenula was sufficient to evoke anhedonia-like behavior. The anhedonia-like behavior induced by CHAT knockdown was not reversed by chronic administration of the selective serotonin reuptake inhibitor fluoxetine. To determine whether habenular cholinergic signaling is associated with regulation of dopamine neurons in the ventral tegmental area (VTA) and serotonin neurons in the dorsal raphe nucleus (DRN), we used CHAT::cre transgenic mice expressing the Designer Receptors Exclusively Activated by Designer Drugs (DREADD). Pharmacogenetic activation of habenular cholinergic neurons induces the excitation of dopamine neurons in the VTA and reduces the immunoreactivity of 5-hydroxytryptamine (5-HT) in the DRN. Habenular cholinergic gene down-regulation was recapitulated in the postmortem habenula of suicide victims diagnosed with major depressive disorder (MDD).
format	article
author	Seungrie Han Soo Hyun Yang Jin Yong Kim Seojung Mo Esther Yang Ki Myung Song Byung-Joo Ham Naguib Mechawar Gustavo Turecki Hyun Woo Lee Hyun Kim
author_facet	Seungrie Han Soo Hyun Yang Jin Yong Kim Seojung Mo Esther Yang Ki Myung Song Byung-Joo Ham Naguib Mechawar Gustavo Turecki Hyun Woo Lee Hyun Kim
author_sort	Seungrie Han
title	Down-regulation of cholinergic signaling in the habenula induces anhedonia-like behavior
title_short	Down-regulation of cholinergic signaling in the habenula induces anhedonia-like behavior
title_full	Down-regulation of cholinergic signaling in the habenula induces anhedonia-like behavior
title_fullStr	Down-regulation of cholinergic signaling in the habenula induces anhedonia-like behavior
title_full_unstemmed	Down-regulation of cholinergic signaling in the habenula induces anhedonia-like behavior
title_sort	down-regulation of cholinergic signaling in the habenula induces anhedonia-like behavior
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/9e4e5fd4bdd14140afe8b403873d4cdf
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Down-regulation of cholinergic signaling in the habenula induces anhedonia-like behavior

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