Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Institute of Maternal and Infant Health, Northwest University, Xi'an 710069, Shaanxi, China.
Department of Neonatology, The First Affiliated Hospital of Medical Xi'an Jiaotong University, Xi'an 710061 Shaanxi, China.
Behav Brain Res. 2022 Aug 26;432:113973. doi: 10.1016/j.bbr.2022.113973. Epub 2022 Jun 18.
Depression is a common mental disease that can lead to suicide when severe. Exposure to prenatal stress (PS) can lead to depression-like behavior in offspring, but the mechanism is unclear. RhoA (Ras homology family member A) plays an important role in stress-induced changes in synaptic plasticity, participating in the development of depression by activating the downstream effector ROCK (Rho-associated protein kinase). This study explored the influence in the expression of RhoA and downstream molecules ROCK1/2 in prenatally stressed rats, and the effect of RhoA inhibitor simvastatin on depression-like behavior induced by PS. Depression-like behavior in offspring was detected by sucrose preference test, forced swimming test, and open-field test. The mRNA and protein expression of RhoA and ROCK1/2 in the hippocampus and prefrontal cortex of offspring rats were detected by qRT-PCR and western blotting, respectively. Our results showed that PS causes depression-like behavior in offspring rats, associated with elevated expression of RhoA, ROCK1/2 in the hippocampus and prefrontal cortex. After administration of simvastatin to PS rats, the expression of RhoA and ROCK2 was significantly reduced, alleviating depression-like behavior. Our study demonstrated that RhoA participates in the depression-like behavior in prenatally stressed offspring rats, which may be a potential target for antidepressant therapy.
抑郁症是一种常见的精神疾病,严重时可能导致自杀。产前应激(PS)可导致后代出现类似抑郁的行为,但机制尚不清楚。RhoA(Ras 同源家族成员 A)在应激诱导的突触可塑性变化中发挥重要作用,通过激活下游效应物 ROCK(Rho 相关蛋白激酶)参与抑郁症的发生。本研究探讨了 RhoA 及其下游分子 ROCK1/2 在产前应激大鼠中的表达变化,以及 RhoA 抑制剂辛伐他汀对 PS 诱导的抑郁样行为的影响。通过蔗糖偏好试验、强迫游泳试验和旷场试验检测后代的抑郁样行为。通过 qRT-PCR 和 Western blot 分别检测子代大鼠海马和前额叶皮质中 RhoA 和 ROCK1/2 的 mRNA 和蛋白表达。结果表明,PS 可导致子代大鼠出现抑郁样行为,与海马和前额叶皮质中 RhoA、ROCK1/2 的表达升高有关。PS 大鼠给予辛伐他汀后,RhoA 和 ROCK2 的表达明显降低,抑郁样行为得到缓解。本研究表明,RhoA 参与产前应激子代大鼠的抑郁样行为,可能成为抗抑郁治疗的潜在靶点。