Heterozygous disruption of beclin 1 alleviates neurotoxicity induced by sub-chronic exposure of arsenite in mice

作者全名："Li, Danyang; Qin, Qizhong; Xia, Yinyin; Cheng, Shuqun; Zhang, Jun; Duan, Xinhao; Qin, Xia; Tian, Xin; Mao, Lejiao; Qiu, Jingfu; Jiang, Xuejun; Zou, Zhen; Chen, Chengzhi"

作者地址："[Li, Danyang; Xia, Yinyin; Cheng, Shuqun; Chen, Chengzhi] Chongqing Med Univ, Sch Publ Hlth, Dept Occupat & Environm Hlth, Chongqing 400016, Peoples R China; [Qin, Qizhong; Jiang, Xuejun] Chongqing Med Univ, Ctr Expt Teaching Publ Hlth, Expt Teaching & Management Ctr, Chongqing 400016, Peoples R China; [Zhang, Jun; Mao, Lejiao; Zou, Zhen] Chongqing Med Univ, Inst Life Sci, Mol Biol Lab Resp Dis, Chongqing 400016, Peoples R China; [Duan, Xinhao; Qiu, Jingfu] Chongqing Med Univ, Dept Hlth Lab Technol, Sch Publ Hlth, Chongqing 400016, Peoples R China; [Qin, Xia] Chongqing Med Univ, Dept Pharm, Affiliated Hosp 1, Chongqing 400016, Peoples R China; [Tian, Xin] Chongqing Med Univ, Dept Neurol, Affiliated Hosp 1, Chongqing, Peoples R China; [Qiu, Jingfu; Jiang, Xuejun; Zou, Zhen; Chen, Chengzhi] Chongqing Med Univ, Res Ctr Environm & Human Hlth, Sch Publ Hlth, Chongqing 400016, Peoples R China; [Zou, Zhen] Chongqing Med Univ, Inst Life Sci, Chongqing 400016, Peoples R China; [Chen, Chengzhi] 1 Yixueyuan Rd, Chongqing 400016, Peoples R China"

通信作者："Jiang, XJ (通讯作者)，Chongqing Med Univ, Ctr Expt Teaching Publ Hlth, Expt Teaching & Management Ctr, Chongqing 400016, Peoples R China.; Zou, Z (通讯作者)，Chongqing Med Univ, Inst Life Sci, Chongqing 400016, Peoples R China.; Chen, CZ (通讯作者)，1 Yixueyuan Rd, Chongqing 400016, Peoples R China."

来源：NEUROTOXICOLOGY

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:000892091700002

JCR分区：Q2

影响因子：3.4

年份：2023

卷号：94

期号：　

开始页：11

结束页：23

文献类型：Article

关键词：Arsenite; Beclin 1; Autophagy; Neurotoxicity

摘要："Arsenite is a well-documented neurotoxicant that widely exists in the environment. However, the detailed mechanisms of arsenite neurotoxicity are not fully clarified. Autophagy has been reported to be involved in many neurological problems induced by arsenite. Since beclin 1 is an essential mediator of autophagy, we herein used both adult wild-type (beclin 1(+/+)) and heterozygous disruption of beclin 1 (beclin 1(+/-)) mice for chronic administration of 50 mg/L arsenite via drinking water for 3 months. Our results demonstrated that exposure of arsenite caused the working memory deficit, anxiety-like behavior and motor coordination disorder in beclin 1(+/ +) mice, accompanied with pathological changes in morphology and electrophysiology in the cortical tissues. This treatment of arsenite significantly reduced the number of neuronal cells and induced microglia activation and synaptic transmission disorders in the wild-type mice as compared with vehicle controls. Intriguingly, by using beclin 1(+/-) mice, we found that heterozygous disruption of beclin 1 profoundly attenuated these neurotoxic effects induced by arsenite, mainly manifested by improvements in the neurobehavioral impairments, abnormal electrophysiologic alterations as well as dysregulation of synaptic transmission. These findings together indicate that regulation of autophagy via beclin 1 would be a potential strategy for treatment against arsenite neurotoxicity."

基金机构："National Natural Science Foundation of China [81602820, 81703187, 81903358, 82001378]; Chongqing Talents: Exceptional Young Talents Project [CQYC2020058650, CQYC2021058941]; Natural Science Foundation of Chongqing [cstc2021ycjh-bgzxm0105, cstc2020jcyj-msxmX0155, cstc2021jcyj-msxmX0141]; Research Program of Basic Research and Frontier Technology of Chongqing Yuzhong district [2020005]; young talent of Bayu scholar"

基金资助正文："This research was supported by National Natural Science Foundation of China (Grant Number: 81602820, 81703187, 81903358, 82001378) , Chongqing Talents: Exceptional Young Talents Project (CQYC2020058650 and CQYC2021058941) , Natural Science Foundation of Chongqing (cstc2021ycjh-bgzxm0105, cstc2020jcyj-msxmX0155 and cstc2021jcyj-msxmX0141) . Research Program of Basic Research and Frontier Technology of Chongqing Yuzhong district (2020005) . J.Z., Z.Z. and C.C were supported by young talent of Bayu scholar."