Citation

Zhou J, Ma Y, Chen J, Yao D, Feng C, Dong Y, Ren Y, Ma H, Wang Z, Li G, Li H, Zhu Z. Behav. Brain Res. 2022; 432: 113973.

Copyright

(Copyright © 2022, Elsevier Publishing)

DOI

10.1016/j.bbr.2022.113973

PMID

35728732

Abstract

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.

Language: en

Keywords

Female; Animals; Pregnancy; Rats; Rats, Sprague-Dawley; Depression-like behavior; *Depression/drug therapy/etiology/metabolism; *Prenatal Exposure Delayed Effects/metabolism; Hippocampus/metabolism; Prenatal stress; rho GTP-Binding Proteins/*metabolism; rho-Associated Kinases/metabolism; RhoA; rhoA GTP-Binding Protein/metabolism; ROCK1/2; Simvastatin; Simvastatin/metabolism; Stress, Psychological/complications/metabolism