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Título : Antidepression action of BDNF requires and is mimicked by Gαi1/3 expression in the hippocampus
Autor : Marshall, John 
Zhou, Xiao-Zhong 
Chen, Gang 
Yang, Su-Qing 
Li, Ya 
Wang, Yin 
Zhang, Zhi-Qing 
Jiang, Qin 
Birnbaumer, Lutz 
Cao, Cong 
Fecha de publicación : 2018
Editorial : National Academy of Sciences
Cita : Marshall J, Zhou X, Chen G, et al. Antidepression action of BDNF requires and is mimicked by Gαi1/3 expression in the hippocampus [en línea]. Proceedings of the National Academy of Sciences. 2018;115(15):E3549–E3558. doi:10.1073/pnas.1722493115 Disponible en:
Resumen : 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.
ISSN : 0027-8424
1091-6490 (online)
Disciplina: MEDICINA
DOI: 10.1073/pnas.1722493115
Derechos: Acceso Abierto
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