GSK-3β may be a factor for restraint stress-induced depression-related behaviors and spatial memory impairment independently of tau phosphorylation

Restraint stress significantly prolonged immobility time in forced swim and tail suspension tests for mice, indicating that restraint stress causes depression-related behaviors. Moreover, restraint stress significantly prolonged the retention latency in the water maze test, indicating that restraint stress causes spatial memory impairment. Phosphorylation of glycogen synthase kinase 3β (GSK-3β) in the hippocampus and hypothalamus from mice with restraint stress was significantly reduced as compared with that for mice without restraint stress, indicating that GSK-3β is activated by restraint stress. In contrast, tau phosphorylation was not affected both in the hippocampus and hypothalamus from mice with restraint stress. Taken together, the results of the present study suggest that GSK-3β is a pivotal factor for stress-induced depression and dementia, independently of tau phosphorylation.