cyclin-d1 and Depressive-Disorder

Depression caused by genetic and environmental factors is acomplicated disease. Here, it is demonstrated that glycogen synthase kinase-3β is highly expressed and phosphorylated in the brain of a chronic stress mouse. Inhibition of glycogen synthase kinase-3βleads to decreased depression-like symptoms which manifest in open-field test, tail-suspension test, forced swim test, and a novelty suppressed feeding test. It was also found that β-catenin is attenuated, and its target genes Cyclin D1 and c-Myc are down-regulated. Glycogen synthase kinase-3β was also found to inhibit Erk-Creb-BDNF signaling. These results show that glycogen synthase kinase-3β may promote the progression of depression. Therefore, targeting glycogen synthase kinase-3β may be an effective therapeutic strategy.

Topics: Animals; Antidepressive Agents; beta Catenin; Brain; Brain-Derived Neurotrophic Factor; Chronic Disease; Cyclin D1; Depressive Disorder; Disease Models, Animal; Feeding Behavior; Glycogen Synthase Kinase 3 beta; Male; Mice, Inbred C57BL; Motor Activity; Phosphorylation; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-myc; Random Allocation; RNA, Messenger; Stress, Psychological; Thiadiazoles