Downregulation of B d nf Expression in Adult Mice Causes Body Weight Gain

Gain or loss of appetite and resulting body weight changes are commonly observed in major depressive disorders (MDDs). Brain-derived neurotrophic factor (BDNF) is broadly expressed in the brain and is thought to play a role in the pathophysiology of MDDs and obesity. Congenital loss of function of BDNF causes weight gain in both humans and rodents; however, it is not clear whether acquired loss of function of BDNF also affects body weight. Thus, we exploited mutant mice in which the Bdnf expression level is regulated by the tetracycline-dependent transcriptional silencer (tTS)-tetracycline operator sequence (tetO) system. Time-controlled Bdnf expression using this system allowed us to establish congenital and acquired loss of function of Bdnf in mice. We demonstrated that changes in Bdnf expression influenced body weight during not only the developmental stage but also the adult stage of mice. Although it is still unclear whether acquired Bdnf loss of function in rodents mimics the pathology of MDD, our findings may bridge the mechanistic gap between MDDs and body weight gain in line with BDNF dysfunction.