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

Lvmei Li; Qiang Wang; Xiangping Sun; ZeLong Li; Shuwei Liu; Xian Zhang; Jinyu Zhou; Rui Zhang; Kunmei Liu; Peng Wang; Jianguo Niu; Yujun Wen; Lianxiang Zhang

doi:10.1016/j.ijbiomac.2023.123652

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

Int J Biol Macromol. 2023 Apr 1:233:123652. doi: 10.1016/j.ijbiomac.2023.123652. Epub 2023 Feb 11.

Authors

Lvmei Li¹, Qiang Wang², Xiangping Sun³, ZeLong Li⁴, Shuwei Liu¹, Xian Zhang⁴, Jinyu Zhou⁵, Rui Zhang⁴, Kunmei Liu⁴, Peng Wang⁴, Jianguo Niu⁶, Yujun Wen⁷, Lianxiang Zhang⁸

Affiliations

¹ Ningxia Key Laboratory of Cerebrocranial Diseases, Incubation Base of the National Key Laboratory, Ningxia Medical University, 1160 Shengli Street, Yinchuan, Ningxia 750004, China; Department of human anatomy and histoembryology, School of Basic Medical Sciences, Ningxia Medical University, 1160 Shengli Street, Yinchuan, Ningxia 750004, China.
² Science - Technology Centers, Ningxia Medical University, 1160 Shengli Street, Yinchuan, Ningxia 750004, China.
³ Department of Surgery, Ningxia Traditional Chinese Medicine Hospital, 114 West Beijing Road, Yinchuan, Ningxia 750021, China.
⁴ Ningxia Key Laboratory of Cerebrocranial Diseases, Incubation Base of the National Key Laboratory, Ningxia Medical University, 1160 Shengli Street, Yinchuan, Ningxia 750004, China.
⁵ Department of Epidemiology and Health Statistics, School of Public Health and Management, Ningxia Medical University, 1160 Shengli Street, Yinchuan, Ningxia 750004, China.
⁶ Ningxia Key Laboratory of Cerebrocranial Diseases, Incubation Base of the National Key Laboratory, Ningxia Medical University, 1160 Shengli Street, Yinchuan, Ningxia 750004, China; Department of human anatomy and histoembryology, School of Basic Medical Sciences, Ningxia Medical University, 1160 Shengli Street, Yinchuan, Ningxia 750004, China. Electronic address: niujg@nxmu.edu.cn.
⁷ Ningxia Key Laboratory of Cerebrocranial Diseases, Incubation Base of the National Key Laboratory, Ningxia Medical University, 1160 Shengli Street, Yinchuan, Ningxia 750004, China; Department of human anatomy and histoembryology, School of Basic Medical Sciences, Ningxia Medical University, 1160 Shengli Street, Yinchuan, Ningxia 750004, China. Electronic address: wenyj@nxmu.edu.cn.
⁸ Ningxia Key Laboratory of Cerebrocranial Diseases, Incubation Base of the National Key Laboratory, Ningxia Medical University, 1160 Shengli Street, Yinchuan, Ningxia 750004, China; Department of human anatomy and histoembryology, School of Basic Medical Sciences, Ningxia Medical University, 1160 Shengli Street, Yinchuan, Ningxia 750004, China. Electronic address: 19940008@nxmu.edu.cn.

PMID: 36780962
DOI: 10.1016/j.ijbiomac.2023.123652

Abstract

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 hippocampus 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 regulated F-actin/G-actin balance and DS plasticity, affecting emotion and cognition.

Keywords: Chronic stress; Cognition; Emotion; Hippocampal synaptic plasticity; Juvenile; RhoA.

MeSH terms

Actin Depolymerizing Factors / metabolism
Actins* / metabolism
Animals
Cognition
Emotions
Hippocampus / metabolism
Neuronal Plasticity
Rats
rhoA GTP-Binding Protein* / genetics
rhoA GTP-Binding Protein* / metabolism

Substances

Actin Depolymerizing Factors
Actins
rhoA GTP-Binding Protein
RhoA protein, rat