Lack of interferon regulatory factor 3 leads to anxiety/depression-like behaviors through disrupting the balance of neuronal excitation and inhibition in mice

Junjie Li; Yayan Pang; Yehong Du; Lei Xia; Mulan Chen; Yepeng Fan; Zhifang Dong

doi:10.1016/j.gendis.2022.05.003

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Lack of interferon regulatory factor 3 leads to anxiety/depression-like behaviors through disrupting the balance of neuronal excitation and inhibition in mice

Full-length article | 更新时间：2023-08-29

- Lack of interferon regulatory factor 3 leads to anxiety/depression-like behaviors through disrupting the balance of neuronal excitation and inhibition in mice
- Lack of interferon regulatory factor 3 leads to anxiety/depression-like behaviors through disrupting the balance of neuronal excitation and inhibition in mice
- Genes & Diseases 2023年10卷第3期
- 作者机构：
  
  Pediatric Research Institute, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Children's Hospital of Chongqing Medical University,Chongqing,China,400014
- 作者简介：
- 基金信息：
- DOI：10.1016/j.gendis.2022.05.003
  中图分类号：
- 纸质出版日期：2023，
  
  网络出版日期：2023-5-1，
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Lack of interferon regulatory factor 3 leads to anxiety/depression-like behaviors through disrupting the balance of neuronal excitation and inhibition in mice[J]. Genes & Diseases, 2023,10(3).

Junjie Li, Yayan Pang, Yehong Du, et al. Lack of interferon regulatory factor 3 leads to anxiety/depression-like behaviors through disrupting the balance of neuronal excitation and inhibition in mice[J]. Genes & Diseases, 2023,10(3).
Lack of interferon regulatory factor 3 leads to anxiety/depression-like behaviors through disrupting the balance of neuronal excitation and inhibition in mice[J]. Genes & Diseases, 2023,10(3). DOI： 10.1016/j.gendis.2022.05.003.

Junjie Li, Yayan Pang, Yehong Du, et al. Lack of interferon regulatory factor 3 leads to anxiety/depression-like behaviors through disrupting the balance of neuronal excitation and inhibition in mice[J]. Genes & Diseases, 2023,10(3). DOI： 10.1016/j.gendis.2022.05.003.

摘要

Abstract

Disrupting the balance of neuronal excitation and inhibition (E/I) is an important pathogenic mechanism of anxiety and depression. Interferon regulatory factor 3 (IRF3) plays a key role in the innate immune response

and activation of

IRF3

triggers the expression of type I interferons and downstream interferon-stimulated genes

which are associated with anxiety and depression. However

whether IRF3 participates in the pathogenesis of anxiety/depression by regulating E/I balance remains poorly understood. Here

we reported that global knockout (KO) of

IRF3

(

IRF3

−/−

) significantly increased anxiety/depression-like behaviors

but did not affect normal spatial learning and memory. Compared with wild type (WT) control mice

the E/I balance was disrupted

as reflected by enhanced glutamatergic transmission and decreased GABAergic transmission in the neurons of hippocampal CA1 and medial prefrontal cortex (mPFC) in

IRF3

-KO mice. Importantly

genetic rescue of IRF3 expression by adeno-associated virus (AAV) was sufficient to alleviate anxiety/depression-like behaviors and restore the neuronal E/I balance in

IRF3

-KO mice. Taken together

our results indicate that IRF3 is critical in maintaining neuronal E/I balance

thereby playing an essential role in ensuring emotional stability.

关键词

Keywords

AnxietyDepressionHippocampusIRF3Medial prefrontal cortexSynaptic transmission

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