Plasma Autoantibodies from Human Diabetic Depression Patients Inhibit Neuritogenesis and Induce Depression-Like Behavior in Mice

Type 2 diabetes mellitus (DM) substantially increases susceptibility to the affective mood disorder depression. However, the underlying mechanism for this association is unclear. Previous studies demonstrated significant associations between autoantibodies (AB) that inhibit neuronal and endothelial function and specific diabetic microvascular complications. In the current study, we tested the hypothesis that diabetic depression AB affect hippocampal neuritogenesis and induce a depression-like phenotype in mice. Diabetic depression AB significantly inhibited bFGF-stimulated PC12 cell process outgrowth (n=12; P<0.001), and hippocampal culture neuritogenesis (n=4; P<0.01) compared to diabetic, no depression AB (n=20) or no AB (n=2), respectively. Diabetic depression AB-mediated inhibition of hippocampal neuritogenesis was significantly (P<0.01) prevented by Y27632, a selective Rho kinase inhibitor (10 µM). Mice (n=16 in each subgroup) given a single intracerebroventricular infusion of diabetic depression pla...