Hijacking Dorsal Raphe to Improve Metabolism and Depression-Like Behaviors via BDNF Gene Transfer in Mice

Author:

Xiu Jianbo12,Han Rongrong12,Liu Zeyue12,Li Jiayu12,Liu Shu12,Shen Yan12,Ding Yu-Qiang3,Xu Qi12ORCID

Affiliation:

1. State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China

2. Neuroscience Center, Chinese Academy of Medical Sciences, Beijing, China

3. State Key Laboratory of Medical Neurobiology and Ministry of Education (MOE) Frontiers Center for Brain Science, Institutes of Brain Science, and Department of Laboratory Animal Science, Fudan University, Shanghai, China

Abstract

Moods and metabolism modulate each other. High comorbidity of depression and metabolic disorders, such as diabetes and obesity, poses a great challenge to treat such conditions. Here we report the therapeutic efficacy of brain-derived neurotrophic factor (BDNF) by gene transfer in the dorsal raphe nucleus (DRN) in a chronic unpredictable mild stress model (CUMS) of depression and models of diabetes and obesity. In CUMS, BDNF-expressing mice displayed antidepressant- and anxiolytic-like behaviors, which are associated with augmented serotonergic activity. Both in the diet-induced obesity model (DIO) and in db/db mice, BDNF ameliorated obesity and diabetes, which may be mediated by enhanced sympathetic activity not involving DRN serotonin. Chronic activation of DRN neurons via chemogenetic tools produced similar effects as BDNF in DIO mice. These results established the DRN as a key nexus in regulating depression-like behaviors and metabolism, which can be exploited to combat comorbid depression and metabolic disorders via BDNF gene transfer.

Publisher

American Diabetes Association

Subject

Endocrinology, Diabetes and Metabolism,Internal Medicine

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