Antidepression action of BDNF requires and is mimicked by Gαi1/3 expression in the hippocampus

Abstract: Stress-related alterations in brain-derived neurotrophic factor (BDNF) expression, a neurotrophin that plays a key role in synaptic plasticity, are believed to contribute to the pathophysiology of depression. Here, we show that in a chronic mild stress (CMS) model of depression the Gαi1 an...

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Autores principales: Marshall, John, Zhou, Xiao-Zhong, Chen, Gang, Yang, Su-Qing, Li, Ya, Wang, Yin, Zhang, Zhi-Qing, Jiang, Qin, Birnbaumer, Lutz, Cao, Cong
Formato: Artículo
Lenguaje:Español
Publicado: National Academy of Sciences 2019
Materias:
DEPRESION
HIPOCAMPO
PROTEINAS
NEURONAS
Acceso en línea:https://repositorio.uca.edu.ar/handle/123456789/8699
Aporte de:
Repositorio Institucional de la Universidad Católica Argentina (UCA) de Universidad Católica Argentina
id I33-R139123456789-8699
record_format dspace
institution Universidad Católica Argentina
institution_str I-33
repository_str R-139
collection Repositorio Institucional de la Universidad Católica Argentina (UCA)
language Español
topic DEPRESION
HIPOCAMPO
PROTEINAS
NEURONAS
spellingShingle DEPRESION
HIPOCAMPO
PROTEINAS
NEURONAS
Marshall, John
Zhou, Xiao-Zhong
Chen, Gang
Yang, Su-Qing
Li, Ya
Wang, Yin
Zhang, Zhi-Qing
Jiang, Qin
Birnbaumer, Lutz
Cao, Cong
Antidepression action of BDNF requires and is mimicked by Gαi1/3 expression in the hippocampus
topic_facet DEPRESION
HIPOCAMPO
PROTEINAS
NEURONAS
description Abstract: Stress-related alterations in brain-derived neurotrophic factor (BDNF) expression, a neurotrophin that plays a key role in synaptic plasticity, are believed to contribute to the pathophysiology of depression. Here, we show that in a chronic mild stress (CMS) model of depression the Gαi1 and Gαi3 subunits of heterotrimeric G proteins are down-regulated in the hippocampus, a key limbic structure associated with major depressive disorder. We provide evidence that Gαi1 and Gαi3 (Gαi1/3) are required for the activation of TrkB downstream signaling pathways. In mouse embryonic fibroblasts (MEFs) and CNS neurons, Gαi1/3 knockdown inhibited BDNF-induced tropomyosin-related kinase B (TrkB) endocytosis, adaptor protein activation, and Akt-mTORC1 and Erk-MAPK signaling. Functional studies show that Gαi1 and Gαi3 knockdown decreases the number of dendrites and dendritic spines in hippocampal neurons. In vivo, hippocampal Gαi1/3 knockdown after bilateral microinjection of lentiviral constructs containing Gαi1 and Gαi3 shRNA elicited depressive behaviors. Critically, exogenous expression of Gαi3 in the hippocampus reversed depressive behaviors in CMS mice. Similar results were observed in Gαi1/Gαi3 double-knockout mice, which exhibited severe depressive behaviors. These results demonstrate that heterotrimeric Gαi1 and Gαi3 proteins are essential for TrkB signaling and that disruption of Gαi1 or Gαi3 function could contribute to depressive behaviors.
format Artículo
author Marshall, John
Zhou, Xiao-Zhong
Chen, Gang
Yang, Su-Qing
Li, Ya
Wang, Yin
Zhang, Zhi-Qing
Jiang, Qin
Birnbaumer, Lutz
Cao, Cong
author_facet Marshall, John
Zhou, Xiao-Zhong
Chen, Gang
Yang, Su-Qing
Li, Ya
Wang, Yin
Zhang, Zhi-Qing
Jiang, Qin
Birnbaumer, Lutz
Cao, Cong
author_sort Marshall, John
title Antidepression action of BDNF requires and is mimicked by Gαi1/3 expression in the hippocampus
title_short Antidepression action of BDNF requires and is mimicked by Gαi1/3 expression in the hippocampus
title_full Antidepression action of BDNF requires and is mimicked by Gαi1/3 expression in the hippocampus
title_fullStr Antidepression action of BDNF requires and is mimicked by Gαi1/3 expression in the hippocampus
title_full_unstemmed Antidepression action of BDNF requires and is mimicked by Gαi1/3 expression in the hippocampus
title_sort antidepression action of bdnf requires and is mimicked by gαi1/3 expression in the hippocampus
publisher National Academy of Sciences
publishDate 2019
url https://repositorio.uca.edu.ar/handle/123456789/8699
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