Central Laboratory, Heze Medical College, Heze, 274000, China.
Maternal and Infant Health Research Institute and Medical College, Northwestern University, Xi'an, 710069, China.
Psychoneuroendocrinology. 2020 May;115:104629. doi: 10.1016/j.psyneuen.2020.104629. Epub 2020 Feb 20.
Prenatal stress (PS) contributes to depression-like behavior in the offspring. PDLIM5 is involved in the onset of mental disorders. This study is to investigate the role and mechanism of PDLIM5 in depression-like behavior of PS offspring rats.
PS model was used to analyze the effects of different treatments to PS offspring rats with different sex, including PDLIM5, PDLIM5 shRNA and 5-aza-2' -deoxycytidine (5-azaD). The depression-like behavior was assessed by the sucrose preference test (SPT) and forced swimming test (FST). The mRNA and protein expression levels of PDLIM5 in the hippocampus of PS offspring rats were detected by qRT-PCR and western blot, respectively. The methylation of PDLIM5 promoter were analyzed by bisulfite sequencing.
Our data revealed that PS offspring rats showed a significant decrease in sucrose preference and a prolonged immobility time. Injection of PDLIM5 significantly improved the depression-like behavior in PS offspring rats, whereas administration of PDLIM5 shRNA aggravated it. In addition, PDLIM5 expression was decreased at the mRNA and protein levels, and the methylation level of PDLIM5 promoter was increased in hippocampus of PS male but not female offspring rats. Furthermore, microinjection of 5-azaD improved the PS induced depression-like behavior in offspring rats. Moreover, in male PS offspring rats, microinjection of 5-azaD reversed the effect of PS on PDLIM5 expression and promoter methylation.
PDLIM5 can significantly improve the depression-like behavior of both male and female PS offspring rats, while the PDLIM5 promoter methylation is only observed in male PS offspring rats. Our study may provide new mechanism for the pathogenesis of depression and experimental evidence for sex-based precise treatment.
产前应激（PS）导致后代出现类似抑郁的行为。PDLIM5 参与精神障碍的发生。本研究旨在探讨 PDLIM5 在 PS 后代大鼠类似抑郁行为中的作用及机制。
采用 PS 模型，分析不同处理方法对不同性别 PS 后代大鼠的影响，包括 PDLIM5、PDLIM5 shRNA 和 5-氮杂-2'-脱氧胞苷（5-azaD）。通过蔗糖偏好试验（SPT）和强迫游泳试验（FST）评估抑郁样行为。采用 qRT-PCR 和 Western blot 分别检测 PS 后代大鼠海马组织中 PDLIM5 的 mRNA 和蛋白表达水平。采用亚硫酸氢盐测序分析 PDLIM5 启动子的甲基化。
研究数据显示，PS 后代大鼠的蔗糖偏好显著降低，不动时间延长。PDLIM5 注射可显著改善 PS 后代大鼠的抑郁样行为，而 PDLIM5 shRNA 给药则加重了这种行为。此外，PDLIM5 在 mRNA 和蛋白水平上的表达降低，且 PS 雄性后代大鼠而非雌性后代大鼠海马组织中 PDLIM5 启动子的甲基化水平升高。此外，5-azaD 微注射可改善后代大鼠的 PS 诱导的抑郁样行为。此外，在 PS 雄性后代大鼠中，5-azaD 微注射逆转了 PS 对 PDLIM5 表达和启动子甲基化的影响。
PDLIM5 可显著改善 PS 雄性和雌性后代大鼠的抑郁样行为，而 PDLIM5 启动子甲基化仅在 PS 雄性后代大鼠中观察到。本研究为抑郁发病机制提供了新的机制，并为基于性别的精准治疗提供了实验证据。
