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

Abstract

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.

Prefrontal cortical trkB, glucocorticoids, and their interactions in stress and developmental contexts

“…However, BDNF and trkB in the frontal cortex, as well as spatial learning and memory in the Morris water maze test, were apparently not affected by stress exposure in the same report. In another study, chronic unpredictable stress reduces Bdnf in the cortex of adult mice, and Bdnf deficiency is detectable 2 weeks following stress, in tandem with decreased sucrose preference and despair-like behavior (Yang et al, 2017). Infusion of an anti-proBDNF antibody into the anterior cingulate cortex reverses all stress-induced behavioral and molecular alterations (for discussion of proBDNF, see section 8.1.1).…”

Oral Probiotics Ameliorate the Behavioral Deficits Induced by Chronic Mild Stress in Mice via the Gut Microbiota-Inflammation Axis

“…The CMS paradigm was performed as previously described ( Yang et al, 2017 ; Nikolova et al, 2018 ), which consisted of the following stressors: cage tilted at 45°(24 h), food and water deprivation (24 h), tail pinch (60 s, 1 cm from the end of the tail), reverse day and night (24 h), overnight stroboscopic lighting (400 flash/min in the dark, 10 h), restraint in a 50-ml plastic syringe tube (2 h), and moist bedding (200 mL of water spilled onto bedding, 8 h) for a total of 4 weeks. The same stressor was not applied on two consecutive days.…”

Beyond good and evil: A putative continuum-sorting hypothesis for the functional role of proBDNF/BDNF-propeptide/mBDNF in antidepressant treatment

“…Intracerebroventricular infusion of adenovirus vector carrying proBDNF sequence increased immobility behavior on FST (Bai et al, 2016). In addition, anti-proBDNF antibody infused into anterior cingulate cortex impeded pro-anxiogenic, pro-depressive and the decrease of cortical and hippocampal BDNF mRNA levels induced by CUS, but anti-BDNF antibody was not able to enhance stress effects (Yang et al, 2017b). Infusion of BDNF into the CA1 area of hippocampus precluded CUSinduced depressive-like behavior, preventing the stress effect of decreasing CA1 hippocampal spine density and the decrease in hippocampal levels of postsynaptic proteins of the excitatory synapse, such as postsynaptic density protein 95, kalirin-7, and NMDA receptor subunit NR2B (Qiao et al, 2017).…”