Underlying mechanisms of recombinant adeno-associated virus-mediated bicaudal C homolog 1 overexpression in the medial prefrontal cortex of mice with induced depressive-like behaviors

Abstract

Bicaudal C homolog 1 gene (BICC1) in the medial prefrontal cortex (mPFC) has been implicated in major depressive disorder (MDD); however, less is known about the mechanisms of BICC1-induced depression. The purpose of the present study was to investigate changes in depressive-like behaviors induced by recombinant adeno-associated virus (rAAV)-mediated overexpression of BICC1 in the mPFC of mice. A viral-mediated genetic approach was employed to explore the BICC1 overexpression-induced depressive-like behavioral and molecular changes in mice. For the first time, we found that BICC1 overexpression significantly induced depressive-like behaviors in mice. Further, the expression of disheveled-2 and the phosphorylation of Ser9 of glycogen synthase kinase 3β (GSK3β), mechanistic target of rapamycin (mTOR) and GluA1, GluA1, brain-derived neurotrophic factor (BDNF), and VGF were markedly down-regulated in BICC1 overexpression-treated animals. Our results demonstrate that the overexpression of BICC1 in the mPFC may induce depressive-like behaviors via GSK3β/mTOR signaling and GluA1 trafficking in the mPFC of mice, indicating that BICC1 may be a potential target for antidepressant treatment.

Keywords: Bicaudal C homolog 1 gene (BICC1); Depression; GSK3β; GluA1; mTOR.