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

作者全名："Li, Junjie; Pang, Yayan; Du, Yehong; Xia, Lei; Chen, Mulan; Fan, Yepeng; Dong, Zhifang"

作者地址："[Li, Junjie; Pang, Yayan; Du, Yehong; Xia, Lei; Chen, Mulan; Fan, Yepeng; Dong, Zhifang] Chongqing Med Univ, Chongqing Key Lab Translat Med Res Cognit Dev & Le, Natl Clin Res Ctr Child Hlth & Disorders, Pediat Res Inst,Minist Educ,Key Lab Child Dev & Di, Chongqing 400014, Peoples R China"

通信作者："Dong, ZF (通讯作者)，Chongqing Med Univ, Chongqing Key Lab Translat Med Res Cognit Dev & Le, Natl Clin Res Ctr Child Hlth & Disorders, Pediat Res Inst,Minist Educ,Key Lab Child Dev & Di, Chongqing 400014, Peoples R China."

来源：GENES & DISEASES

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001017463800001

JCR分区：Q1

影响因子：6.8

年份：2023

卷号：10

期号：3

开始页：1062

结束页：1074

文献类型：Article

关键词：Anxiety; Depression; Hippocampus; IRF3; Medial prefrontal cortex; Synaptic transmission

摘要："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. & COPY; 2022 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons. org/licenses/by-nc-nd/4.0/)."

基金机构："National Natural Science Foundation of China [82071395and 82001158]; Natural Science Foundation of Chongqing, China [cstc2021ycjh-bgzxm0186, cstc2020jcyj-zdxmX0004]; Science and Technology Research Program of Chongqing Municipal Education Commission, China [KJZD-K201900403]; Innovation Research Group at Institutions of Higher Education in Chongqing, China [CXQTP19034]; CQMU Program for Youth Innovation in Future Medicine, China [W0044]"

基金资助正文："This work was supported by grants from the National Natural Science Foundation of China (No. 82071395and 82001158) , the Natural Science Foundation of Chongqing, China (No. cstc2021ycjh-bgzxm0186 and cstc2020jcyj-zdxmX0004) , the Science and Technology Research Program of Chongqing Municipal Education Commission, China (No. KJZD-K201900403) , Innovation Research Group at Institutions of Higher Education in Chongqing, China (No. CXQTP19034) and CQMU Program for Youth Innovation in Future Medicine, China (No. W0044) ."