Increased Glycogen Synthase Kinase-3β mRNA Level in the Hippocampus of Patients with Major Depression: A Study Using the Stanley Neuropathology Consortium Integrative Database

OBJECTIVE Glycogen synthase kinase-3β (GSK-3β) has become recognized as a broadly influential enzyme affecting diverse range of biological functions, including gene expression, cellular architecture, and apoptosis. The results of previous studies suggest that GSK-3β activity may be increased in the brain of patients with major depressive disorders (MDD). A recent animal study reported increased GSK-3β messenger ribonucleic acid (mRNA) level in the hippocampus of those with depression. However, few studies have investigated GSK-3β activity in the brain of patients with MDD. METHODS In order to test whether patients with MDD have an increase in GSK-3β activity in the brain compared to normal controls, we explored GSK-3β expression level in all brain regions by using the Stanley Neuropathology Consortium Integrative Database (SNCID), which is a web-based method of integrating the Stanley Medical Research Institute data sets. RESULTS The level of GSK-3β mRNA expression in the hippocampus was significantly increased in the MDD group (n=8) compared with the control group (n=12, p<0.05). Spearman's test also reveals that GSK-3β mRNA expression levels were significantly correlated with nitric oxide synthase 1 (NOS1)(ρ=0.70, p<0.0001) and stathmin-like 3 (STMN3)(ρ=0.70, p<0.0001) in the hippocampus. CONCLUSION Our results correspond with the results of previous animal studies that reported increased GSK-3β activity in the hippocampus of those with depression. Our findings also suggest that oxidative stress-induced neuronal cell death and abnormal synaptic plasticity in the hippocampus may play important roles in the pathophysiology of major depression.