The altered change of Notch1 signaling in depressed rats

Objective To investigate the relationship between impaired hippocampal neurogenesis and altered Notch1 signaling in depressed rats.Methods In the present study,chronic unpredictable mild stress(CUMS) was used to inhibit the neurogenesis in the hippocampus.The function of Notch1 signaling was investigated by using real-time PCR and western blot at different time points(14 d and 28 d) during chronic stress.The hippocampal neurogenesis was monitored by assessing cell proliferation,survival,and differentiation.Results After 14 days,CUMS significantly reduced weight(P 0.05),the sucrose preference(P 0.001),number of squares crossed(P 0.01) and number of grooming and rearing compared with the controls.The immobility time was significantly increased after 14 d CUMS treated relative to the controls(P 0.001).Twenty-eight days after CUMS protocol,these parameters were significantly difference in rats exposed to CUMS compare with the controls(weight,P 0.05;sucrose preference,P 0.001;number of squares crossed,P 0.001;number of grooming and rearing,P 0.001;and immobility time,P 0.001).During stress,the cell proliferation and survival in DG were decreased compared with the control(P 0.001).The mRNA and protein levels of Notch1 signaling components(NICD,Hes 1,Hes 5,Jag 1) in the hippocampus decreased during stress(P 0.001).Conclusions These results suggest that chronic stress reduce Notch1 signaling function in the hippocampus and the down-regulation of the Notch1 pathway caused by chronic stress might partly contribute to decreased neurogenesis in the hippocampus.