The Expression of Prostate Apoptosis Response-4 in Striatum of A Rat Model of Depression Induced by Chronic Stress

Abstract

Chronic stress may induce depression, but the mechanism is unclear. Previous studies suggested that dopamine system, especially dopamine receptor D2 (DRD2) may be involved in, and prostate apoptosis response-4 (par-4) may be the link point between DRD2 and depression. The aims of this research are to detect the expression of par-4 in striatum of a rat model of depression induced by chronic stress, and to explore whether DNA methylaion is involved in the regulatory mechanism of par-4 expression. Newborn rats were randomly divided into two groups, when they grew up to ten weeks, the experimental group rats (n = 17) accepted chronic mild stress for 3 weeks, while the control group rats (n = 17) received no experimental handle. Their depressive level was assessed with forced swimming test and sucrose consumption test; the mRNA expression of par-4 and DRD2 in rats’ striatum was detected by Real-Time PCR; the protein expression of par-4 was detected by western blot; and the DNA methylation level of par-4 was investigated by bisulfated DNA sequencing. The result showed that the float time of experimental rats was longer than the control rats (t = 4.01, p 0.05), and the sucrose preference rate of experimental rats was reduced compare with the control rats (t = -2.93, p 0.05). The par-4 and DRD2 mRNA expression of experimental rats were lower than the control rats (t values were -3.56 and -2.507 respectively, p 0.05), and the fold changes of par-4 and DRD2 mRNA expression in experimental rats compared to control rats were 0.33 and 0.33 respectively. The par-4 protein expression of experimental rats was decreased compared with the control rats (t = -4.92, p 0.05). However, there was no significant difference between two groups in methylation level of par-4 promoter region (t = -0.26, p 0.05). These results suggest that chronic mild stress could induce the depressive behaviors of rats and suppress the expression of par-4, but DNA methylation seems to be not involved in the regulatory mechanism.