Chronic restraint stress induces changes in the cerebral Galpha 12/13 and Rho-GTPase signaling network

Background Evidence indicates that G alpha 12, G alpha 13, and its downstream effectors, RhoA and Rac1, regulate neuronal morphology affected by stress. This study was aimed at investigating whether repeated stress influences the expression of proteins related to the G alpha 12/13 intracellular signaling pathway in selected brain regions sensitive to the effects of stress. Furthermore, the therapeutic impact of beta(1)adrenergic receptors (beta 1AR) blockade was assessed. Methods Restraint stress (RS) model in mice (2 h/14 days) was used to assess prolonged stress effects on the mRNA expression of G alpha 12, G alpha 13, RhoA, Rac1 in the prefrontal cortex (PFC), hippocampus (HIP) and amygdala (AMY). In a separate study, applying RS model in rats (3-4 h/1 day or 14 days), we evaluated stress effects on the expression of G alpha 12, G alpha 11, G alpha q, RhoA, RhoB, RhoC, Rac1/2/3 in the HIP. Betaxolol (BET), a selective beta 1AR antagonist, was introduced (5 mg/kg/p.o./8-14 days) in the rat RS model to assess the role of beta 1AR in stress effects. RT-qPCR and Western Blot were used for mRNA and protein assessments, respectively. Results Chronic RS decreased mRNA expression of G alpha 12 and increased mRNA for Rac1 in the PFC of mice. In the mice AMY, decreased mRNA expression of G alpha 12, G alpha 13 and RhoA was observed. Fourteen days of RS exposure increased RhoA protein level in the rats' HIP in the manner dependent on beta 1AR activity. Conclusions Together, these results suggest that repeated RS affects the expression of genes and proteins known to be engaged in neural plasticity, providing potential targets for further studies aimed at unraveling the molecular mechanisms of stress-related neuropsychiatric diseases.

Automated summary

This study found that chronic repeated stress affects the expression of proteins related to the G alpha 12/13 signaling pathway in the brain, with beta 1AR blockade showing potential therapeutic effects. These findings provide insight into the molecular mechanisms of stress-related neuropsychiatric diseases.