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

ABSTRACT

OBJECTIVE: Glycogen synthase kinase-3beta (GSK-3beta) 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-3beta activity may be increased in the brain of patients with major depressive disorders (MDD). A recent animal study reported increased GSK-3beta messenger ribonucleic acid (mRNA) level in the hippocampus of those with depression. However, few studies have investigated GSK-3beta activity in the brain of patients with MDD. METHODS: In order to test whether patients with MDD have an increase in GSK-3beta activity in the brain compared to normal controls, we explored GSK-3beta 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-3beta 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-3beta mRNA expression levels were significantly correlated with nitric oxide synthase 1 (NOS1)(rho=0.70, p<0.0001) and stathmin-like 3 (STMN3)(rho=0.70, p<0.0001) in the hippocampus. CONCLUSION: Our results correspond with the results of previous animal studies that reported increased GSK-3beta 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.