Gsk3β aggravates the depression symptoms in chronic stress mouse model

Abstract

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.

Keywords: BDNF pathway; Gsk3β; Wnt pathway; behavioral testing; chronic stress mouse model; depression.