Activation of RhoA pathway participated in the changes of emotion, cognitive function and hippocampal synaptic plasticity in juvenile chronic stress rats

Neuropsychiatric diseases are related to early life stress (ELS), patients often have abnormal learning, memory and emotion. But the regulatory mechanism is unclear. Hippocampal synaptic plasticity (HSP) changes are important mechanism. RhoA pathway is known to regulate HSP by modulating of dendritic spines (DS), whether it's involved in HSP changes in ELS hasn't been reported. So we investigated whether and how RhoA participates in HSP regulation in ELS. The ELS model was established by separation-rearing in juvenile. Results of IntelliCage detection etc. showed simple learning and memory wasn't affected, but spatial, punitive learning and memories reduced, the desire to explore novel things reduced, the anxiety-like emotion increased. We further found hip-pocampus was activated, the hippocampal neurons dendritic complexities reduced, the proportion of mature DS decreased. The full-length transcriptome sequencing techniques was used to screen for differentially expressed genes involved in regulating HSP changes, we found RhoA gene was up-regulated. We detected RhoA protein, RhoA phosphorylation and downstream molecules expression changes, results shown RhoA and p-RhoA, p-ROCK2 expression increased, p-LIMK, p-cofilin expression and F-actin/G-actin ratio decreased. Our study revealed HSP changes in ELS maybe regulate by activation RhoA through ROCK2/LIMK/cofilin pathway regu-lated F-actin/G-actin balance and DS plasticity, affecting emotion and cognition.

Automated summary

Neuropsychiatric diseases are associated with early life stress (ELS) and patients often exhibit abnormal learning, memory, and emotion. The regulatory mechanism underlying these conditions remains unclear. Hippocampal synaptic plasticity (HSP) changes play an important role, and the RhoA pathway is known to regulate HSP through the modulation of dendritic spines (DS). However, the involvement of RhoA in HSP changes in ELS has not been reported. In this study, we investigated the participation and mechanisms of RhoA in HSP regulation in ELS.