Vitamin D binding protein in ventral CA3 of the hippocampus drives stress-induced depression

However, the molecular mechanism underlying its dysfunction in the pathogenesis of major depressive disorder (MDD) is still elusive. Here, we found increased expression of vitamin D binding protein (VDBP) in the hippocampi of MDD patients and chronic unpredictable mild stress (CUMS) susceptible mice, which was correlated with the severity of depression-like behaviors in mice.

Specifically, hippocampal VDBP upregulation was restricted to the glutamatergic neurons in the ventral Cornu Ammonis 3 (vCA3) region of CUMS-susceptible mice. Recombinant adeno-associated virus (rAAV)-mediated VDBP overexpression in vCA3 glutamatergic neurons induced depression-like behaviors in mice, accompanied by impaired neuronal structure and activities, whereas VDBP-targeted knockdown increased the resilience to CUMS.