Your browser doesn't support javascript.
loading
Chronic social isolation leads to abnormal behavior in male mice through the hippocampal METTL14 mediated epitranscriptomic RNA m6A modifications.
Xu, Xiao Fan; Chen, Jie; Long, Lu Hong; Zhang, Ao Mei; Yang, Jing Wen; Li, Yu Jia; Chen, Ling; Zhong, Xiao Lin; Xu, Yang; Cao, Wen Yu.
Afiliação
  • Xu XF; Clinical Anatomy & Reproductive Medicine Application Institute, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China; Department of Neurosurgery, Liaocheng People's Hospital, Liaocheng 252000, Shandong, China.
  • Chen J; Clinical Anatomy & Reproductive Medicine Application Institute, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China.
  • Long LH; Clinical Anatomy & Reproductive Medicine Application Institute, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China.
  • Zhang AM; Clinical Anatomy & Reproductive Medicine Application Institute, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China.
  • Yang JW; Clinical Anatomy & Reproductive Medicine Application Institute, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China.
  • Li YJ; Institute of Neuroscience, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, China.
  • Chen L; Institute of Clinical Medicine, The First Affiliated Hospital of University of South China, 421001 Hengyang, Hunan, China.
  • Zhong XL; Institute of Clinical Medicine, The First Affiliated Hospital of University of South China, 421001 Hengyang, Hunan, China.
  • Xu Y; Institute of Neuroscience, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, China. Electronic address: xuyang2117@163.com.
  • Cao WY; Clinical Anatomy & Reproductive Medicine Application Institute, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China. Electronic address: cwy@usc.edu.cn.
J Affect Disord ; 366: 262-272, 2024 Dec 01.
Article em En | MEDLINE | ID: mdl-39209273
ABSTRACT

BACKGROUND:

Social isolation not only increases the risk of mortality in later life but also causes depressive symptoms, cognitive and physical disabilities. Although RNA m6A modifications are suggested to play key roles in brain development, neuronal signaling and neurological disorders, both the roles of m6A and the enzymes that regulate RNA m6A modification in social isolation induced abnormal behavior is unknown. The present study aims to explore the possible epitranscriptomic role of RNA m6A modifications and its enzymes in social isolation induced impaired behavior.

METHODS:

3-4 weeks mice experiencing 8 weeks social isolation stress (SI) were used in the present study. We quantified m6A levels in brain regions related to mood and cognitive behavior. And the expression of hippocampal m6A enzymes was also determined. The role of hippocampal m6A and its enzymes in SI induced abnormal behavior was further verified by the virus tool.

RESULTS:

SI led to not only depressive and anxiety-like behaviors but also cognitive impairment, with corresponding decreases in hippocampal m6A and METTL14. Hippocampal over-expression METTL14 with lentivirus not only rescued these behaviors but also enhanced the hippocampal m6A level. Hippocampal over-expression METTL14 resulted in increased synaptic related genes.

CONCLUSIONS:

We provide the first evidence that post-weaning social isolation reduces hippocampal m6A level and causes altered expression of m6A enzyme in mice. Importantly, hippocampal METTL14 over-expression alleviated the SI-induced depression/anxiety-like and impaired cognitive behaviors and enhanced m6A level and synaptic related genes expression.
Assuntos
Palavras-chave
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Isolamento Social / Hipocampo / Metiltransferases Limite: Animals Idioma: En Revista: J Affect Disord Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China País de publicação: Holanda
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Isolamento Social / Hipocampo / Metiltransferases Limite: Animals Idioma: En Revista: J Affect Disord Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China País de publicação: Holanda