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

Diabetes
Jianbo XiuQi Xu

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.

References

Nov 22, 1991·The Journal of Comparative Neurology·R P Vertes
Feb 1, 1994·The Journal of Comparative Neurology·R P Vertes, B Kocsis
Jan 1, 1997·Pharmacology, Biochemistry, and Behavior·J A SiuciakR M Lindsay
May 14, 1998·Journal of Neuroscience Research·J A SiuciakA F Russo
Dec 28, 1999·Proceedings of the National Academy of Sciences of the United States of America·W E LyonsL Tessarollo
Sep 27, 2000·Proceedings of the National Academy of Sciences of the United States of America·A M Magariños, B S McEwen
Aug 1, 2006·Progress in Brain Research·Ronald M Lechan, Csaba Fekete
Oct 19, 2010·Nature Medicine·Vanja DuricRonald S Duman
Feb 25, 2011·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Emily E NobleChuanFeng Wang
Oct 9, 2012·Science·Ronald S Duman, George K Aghajanian
Feb 8, 2014·Nature Reviews. Cancer·Sarah Seton-Rogers
Feb 6, 2015·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Vitaly RyuTimothy J Bartness
Feb 13, 2015·Proceedings of the National Academy of Sciences of the United States of America·Benjamin D SachsMarc G Caron
May 23, 2015·The Lancet. Diabetes & Endocrinology·Calum D MoultonKhalida Ismail
Sep 19, 2015·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Daniel J UrbanBryan L Roth
Dec 9, 2015·Proceedings of the National Academy of Sciences of the United States of America·Miriam E BocarslyElizabeth Gould
Dec 15, 2015·Cell Reports·Anne TeissierMark S Ansorge
Jan 28, 2016·Nature Neuroscience·Michael J KrashesAlastair S Garfield
Apr 8, 2016·Nature Reviews. Neuroscience·Baoji Xu, Xiangyang Xie
Oct 21, 2016·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Megumi AdachiLisa M Monteggia
Jul 29, 2017·Cell·Alexander R NectowJeffrey M Friedman
Feb 18, 2018·Molecular Psychiatry·Yuri MilaneschiBrenda Wjh Penninx
Aug 7, 2018·Sleep Medicine·Christelle PeyronPierre-Hervé Luppi
Jul 24, 2020·Nature·Putianqi WangJeffrey Friedman

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