Effects of GSK-3β/β-catenin signaling pathway in chronic sleep deprivation-induced anxiety- and depression-like behaviors of mice / 中华行为医学与脑科学杂志

ABSTRACT

Objective:To explore the modulatory effects of GSK-3β/β-catenin signaling pathway on anxiety- and depression-like behavior of mice induced by chronic sleep deprivation (CSD).Methods:Forty-eight 10-week-old C57BL/6J male mice were selected and randomly divided into four groups(with 12 mice in each group) control group, inhibitor-only group (LiCl), chronic sleep deprivation group (CSD) and inhibitor with CSD group (LiCl+ CSD). Elevated plus maze (EPM) and forced swimming test (FST) were used to evaluate the behavior of mice, HE staining was used to observe the pathological morphological changes of hippocampal neurons, and Western blot was used to detect the protein expressions of β-catenin, GSK-3β and p-GSK-3β in hippocampal tissues. SPSS 22.0 software was used for independent sample t-test and one way ANOVA. Results:After modeling, the body weight of mice in the CSD group ((26.53±0.76)g) was significantly lower than that of the control group ((28.00±0.37)g) ( q=4.119, P=0.041), and the body weight in the LiCl+ CSD group ((28.04±0.86)g) was improved compared with CSD group ( q=4.240, P=0.036). In EPM, the ratio of the entering times and the proportion of the staying time in the open arm in the CSD group ((48.44±9.16)%) and ((16.47±10.42)%) were significantly lower than those in the control group ((68.92±11.71)% and (42.93±15.89)%) ( q=4.660, P=0.018, q=4.346, P=0.029), but the staying time in the open arm in the LiCl+ CSD group ((32.92±12.05)%) was significantly higher than that in the CSD group ( q=2.432, P=0.038). In FST, the percentage of floating immobility time of the mice in the CSD group ((55.00±5.36)%) was significantly longer than that of the control group ((39.95±2.87)%) ( P=0.023), which was decreased significantly in the LiCl+ CSD group ((42.00±7.92)%) than that in the CSD group ( P=0.040). Western blot results showed that, the expressions of p-GSK-3β and β-catenin in the hippocampus of CSD group were decreased significantly ( P=0.040, P=0.008), while the expression of GSK-3β was significantly increased than that of the control group ( P<0.001). Both p-GSK-3β and β-catenin were significantly reversed in CSD+ LiCl group than that in CSD ( P=0.034, P=0.038). Conclusion:The GSK-3β/β-catenin signaling pathway may be involved in the regulation of CSD-induced anxiety and depression-like behaviors in mice.