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Alteration of twinfilin1 expression underlies opioid withdrawal-induced remodeling of actin cytoskeleton at synapses and formation of aversive memory

文献类型：期刊论文

作者Wang, Yu-Jun1; Yu, Chuan1; Wu, Wei-Wei1; Ju, Yun-Yue1; Liu, Yao1; Xu, Chi2; Long, Jian-Dong1; Zan, Gui-Ying1; Wei, Xiang-Yan3; Zhang, Le-Sha1
刊名MOLECULAR PSYCHIATRY
出版日期2021-05-07
页码19
ISSN号1359-4184
DOI10.1038/s41380-021-01111-3
通讯作者Wang, Yu-Jun(yjwang@mail.simm.ac.cn) ; Chen, Zhong(chenzhong@zju.edu.cn) ; Liu, Jing-Gen(jgliu@simm.ac.cn)
英文摘要Exposure to drugs of abuse induces alterations of dendritic spine morphology and density that has been proposed to be a cellular basis of long-lasting addictive memory and heavily depend on remodeling of its underlying actin cytoskeleton by the actin cytoskeleton regulators. However, the actin cytoskeleton regulators involved and the specific mechanisms whereby drugs of abuse alter their expression or function are largely unknown. Twinfilin (Twf1) is a highly conserved actin-depolymerizing factor that regulates actin dynamics in organisms from yeast to mammals. Despite abundant expression of Twf1 in mammalian brain, little is known about its importance for brain functions such as experience-dependent synaptic and behavioral plasticity. Here we show that conditioned morphine withdrawal (CMW)-induced synaptic structure and behavior plasticity depends on downregulation of Twf1 in the amygdala of rats. Genetically manipulating Twf1 expression in the amygdala bidirectionally regulates CMW-induced changes in actin polymerization, spine density and behavior. We further demonstrate that downregulation of Twf1 is due to upregulation of miR101a expression via a previously unrecognized mechanism involving CMW-induced increases in miR101a nuclear processing via phosphorylation of MeCP2 at Ser421. Our findings establish the importance of Twf1 in regulating opioid-induced synaptic and behavioral plasticity and demonstrate its value as a potential therapeutic target for the treatment of opioid addiction.
WOS关键词AMPA RECEPTOR TRAFFICKING ; NUCLEUS-ACCUMBENS ; DENDRITIC SPINES ; MOUSE MODEL ; SYNAPTIC PLASTICITY ; BINDING PROTEIN ; DRUG-WITHDRAWAL ; COCAINE INTAKE ; MICRORNA ; MECP2
资助项目National Natural Science Foundation of China[81130087] ; National Natural Science Foundation of China[81671322] ; National Natural Science Foundation of China[81773710] ; Ministry of Sciences and Technology of China[2015CB553502] ; Youth Innovation Promotion Association of the Chinese Academy of Sciences[2017334]
WOS研究方向Biochemistry & Molecular Biology ; Neurosciences & Neurology ; Psychiatry
语种英语
出版者SPRINGERNATURE
WOS记录号WOS:000648219000007
源URL[http://119.78.100.183/handle/2S10ELR8/296651]  
专题中国科学院上海药物研究所
通讯作者Wang, Yu-Jun; Chen, Zhong; Liu, Jing-Gen
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, Key Lab Receptor Res, Shanghai, Peoples R China
2.Zhejiang Chinese Med Univ, Clin Coll 3, Dept Neurobiol & Acupuncture Res, Key Lab Acupuncture & Neurol Zhejiang Prov, Hangzhou, Peoples R China
3.Shanghai Univ Tradit Chinese Med, Sch Pharm, Shanghai, Peoples R China
推荐引用方式
GB/T 7714		 Wang, Yu-Jun,Yu, Chuan,Wu, Wei-Wei,et al. Alteration of twinfilin1 expression underlies opioid withdrawal-induced remodeling of actin cytoskeleton at synapses and formation of aversive memory[J]. MOLECULAR PSYCHIATRY,2021:19.
APA Wang, Yu-Jun.,Yu, Chuan.,Wu, Wei-Wei.,Ju, Yun-Yue.,Liu, Yao.,...&Liu, Jing-Gen.(2021).Alteration of twinfilin1 expression underlies opioid withdrawal-induced remodeling of actin cytoskeleton at synapses and formation of aversive memory.MOLECULAR PSYCHIATRY,19.
MLA Wang, Yu-Jun,et al."Alteration of twinfilin1 expression underlies opioid withdrawal-induced remodeling of actin cytoskeleton at synapses and formation of aversive memory".MOLECULAR PSYCHIATRY (2021):19.

入库方式： OAI收割

来源：上海药物研究所

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