Injection of Anti-proBDNF in Anterior Cingulate Cortex (ACC) Reverses Chronic Stress-Induced Adverse Mood Behaviors in Mice.

Foraging behavior is a species-specific behavior which is considered to involve the decision making and higher cognitive functions. We previously established a novel method to detect the foraging behavior in chronic unpredictable mild stress (CUMS)-induced depression mice, in which the food foraging activity of mice was significantly reduced. Furthermore, it is generally assumed that the bilateral anterior cingulate cortex (ACC) is related to foraging activity in rat. Brain-derived neurotrophic factor (BDNF) is widely expressed in many regions of the brain and is down-regulated in depressive patients. However, the relationship between the precursor of brain-derived neurotrophic factor (proBDNF) and depression has not been fully elucidated. The results showed that CUMS in mice induced anxiety- and depression-like behaviors and significant reduction in BDNF messenger RNA (mRNA) in the brain. In this study, we evaluated the effect of anti-BDNF and anti-proBDNF in the ACC on the CUMS-induced depression mice. In contrast to the normal IgG group (normal IgG microinjection into the ACC), bilateral ACC treatment with anti-proBDNF microinjection not only reversed depressive activity but also significantly increased the amount of foraged food and BDNF mRNA in the brain. There was no significant alteration in the group of anti-BDNF microinjection into the ACC. Our data indicate that the proBDNF signaling pathway might down-regulate the foraging activity in CUMS rodents and be involved in the depression.