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

• Autores: Marshall, John; Zhou, Xiao-Zhong; Chen, Gang; Yang, Su-Qing; Li, Ya; Wang, Yin; Zhang, Zhi-Qing; Jiang, Qin; Birnbaumer, Lutz; Cao, Cong
• Año de publicación: 2018
• Idioma: español castellano
• Tipo de recurso: artículo
• Fuente: Proceedings of the National Academy of Sciences. 2018;115(15):E3549–E3558
• Materia: DEPRESION; HIPOCAMPO; PROTEINAS; NEURONAS
• Institución: Pontificia Universidad Católica Argentina

Fil: Marshall, John. Brown University. Department of Molecular Pharmacology, Physiology, and Biotechnology; Estados Unidos
Fil: Zhou, Xiao-Zhong. Soochow University. Jiangsu Key Laboratory of Neuropsychiatric Diseases Research; China
Fil: Zhou, Xiao-Zhong. Soochow University. Institute of Neuroscience; China
Fil: Zhou, Xiao-Zhong. Second Affiliated Hospital of Soochow University. Department of Orthopedics; China
Fil: Chen, Gang. First Affiliated Hospital of Soochow University. Department of Neurosurgery; China
Fil: Yang, Su-Qing. Soochow University. Jiangsu Key Laboratory of Neuropsychiatric Diseases Research; China
Fil: Yang, Su-Qing. Soochow University. Institute of Neuroscience; China
Fil: Li, Ya. Jiangsu Key Laboratory of Neuropsychiatric Diseases Research; China
Fil: Li, Ya. Soochow University. Institute of Neuroscience; China
Fil: Wang, Yin. Jiangsu Key Laboratory of Neuropsychiatric Diseases Research; China
Fil: Wang, Yin. Soochow University. Institute of Neuroscience; China
Fil:Zhang, Zhi-Qing. Jiangsu Key Laboratory of Neuropsychiatric Diseases Research; China
Fil:Zhang, Zhi-Qing. Soochow University. Institute of Neuroscience; China
Fil: Jiang, Qin. Nanjing Medical University. The Affiliated Eye Hospital. The Fourth School of Clinical Medicine; China
Fil: Birnbaumer, Lutz. National Institute of Environmental Health Sciences. Neurobiology Laboratory; Estados Unidos
Fil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina
Fil: Cao, Cong. Jiangsu Key Laboratory of Neuropsychiatric Diseases Research; China
Fil: Cao, Cong. Soochow University. Institute of Neuroscience; China
Fil: Cao, Cong. Nanjing Medical University. The Affiliated Eye Hospital. The Fourth School of Clinical Medicine; China
Fil: Cao, Cong. The Municipal Hospital of Suzhou. North District; China
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.