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Download fileHijacking Dorsal Raphe to Improve Metabolism and Depression-like Behaviors via BDNF Gene Transfer in Mice
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posted on 2021-06-08, 14:21 authored by Jianbo Xiu, Rongrong Han, Zeyue Liu, Jiayu Li, Shu Liu, Yan Shen, Yu-Qiang Ding, Qi XuMoods and metabolism modulate each other. High
comorbidity of depression and metabolic disorders such as diabetes and obesity
poses a great challenge to treat such condition. 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 of
depression (CUMS) 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.