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

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