Regulating effects of GSK650394 on behavior and hippocampal neurotrophy in chronic stress model of depression in rats

doi:10.16352/j.issn.1001-6325.2022.01.013

Abstract

Abstract: Objective To investigate the protective effect of serum and glucocorticoid-regulated kinase 1(SGK1) inhibitor GSK650394 on depression-like behaviors and hippocampus neurotrophy in depressive model rats. Methods SD rats were randomly divided into control group, depression model group and GSK650394 group. Depression model was established by chronic mild unpredictable stress. The behavioral changes of the SD rats were observed by forced swimming, 1% sugar consumption test and Morris water maze. The changes of corticosterone(CORT) and monoamine neurotransmitters in plasma and serum were observed by ELISA. The changes of BDNF, NT-3 and NGF in hippocampus were detected by Western blot. Results Compared with the control group, the model group showed that sucrose preference decreased and swimming immobility time increased significantly(P＜0.01). Escape latency(EL) and latency time(Lat.T) prolonged significantly (P＜0.05 or P＜0.01) and the content of CORT in plasma increased significantly (P＜0.01). The content of 5-HT, NE in serum and the expression of BDNF, NT-3, NGF in hippocampus significant increased in the model group. Compared with model group, GSK650394 significantly increased sucrose preference, decreased immobility time(P＜0.05 or P＜0.01), shortened EL and Lat.T(P＜0.05), decreased the content of CORT in plasma (P＜0.01) and enhanced the level of 5-HT and NE in serum (P＜0.01) and also promoted the expression of NT-3, BDNF and NGF in hippocampus. Conclusions SGK1 inhibitor GSK650394 can significantly relieve depression like behavior potentially through improving the nutrition profile of neurotrophin in hippocampus.

Key words: depression, glucocorticoid-regulated kinase 1(SGK1), GSK650394, hippocampus, neurotrophin

CLC Number:

R749.4

LIU Dan, LIN Xiao-yuan, YANG Hui, LIU Tong-tong, LIU Ping-an, MENG Pan. Regulating effects of GSK650394 on behavior and hippocampal neurotrophy in chronic stress model of depression in rats[J]. Basic & Clinical Medicine, 2022, 42(1): 89-93.

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