title: Epigenetic upregulation of alpha-synuclein in the rats exposed to methamphetamine.
abstract: Abuse of methamphetamine (METH) increases the risk of occurrence of Parkinson׳s disease (PD) in the individuals. Increased expression of synaptic protein α-synuclein (encoded by gene Snca) is remarkably associated with the neuronal loss and motor dysfunction in the patients with PD. The present study aimed to explore the epigenetic mechanism underlying the altered expression of α-synuclein in substantia nigra in the rats previously exposed to METH. Exposure to METH induced significant behavioral impairments in the rotarod test and open field test, as well as the upregulation of cytokine synthesis in the substantia nigra. Significantly increased expression of α-synuclein was also observed in the substantia nigra in the rats exposed to METH. Further chromatin immunoprecipitation and bisulfite sequencing studies revealed a significantly decreased cytosine methylation in the Snca promoter region in the rats exposed to METH. It was found that the occupancy of methyl CpG binding protein 2 and DNA methyltransferase 1 in Snca promoter region was also significantly decreased in the substantia nigra in the modeled rats. These results advanced our understanding on the mechanism of the increased incidence of PD in the individuals with history use of METH, and shed novel lights on the development of therapeutic approaches for the patients conflicted with this neurological disorder.
authors.affiliation: Department of Neurology Fist Affiliated Hospital of Liaoning Medical University, 5-2 Renmin Street, Jinzhou, Liaoning 121000, China. Electronic address: jiangwenda01@163.com.
authors.forename: Wenda
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Department of Neurology Fist Affiliated Hospital of Liaoning Medical University, 5-2 Renmin Street, Jinzhou, Liaoning 121000, China.
authors.forename: Ji
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Neurology Fist Affiliated Hospital of Liaoning Medical University, 5-2 Renmin Street, Jinzhou, Liaoning 121000, China.
authors.forename: Zhuang
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Institute of Medicine Liaoning Medical University, Jinzhou 121000, China.
authors.forename: Hongxin
authors.initials: H
authors.lastname: Wang
authors.affiliation: Dalian Medical University, Dalian, Liaoning 116044, China.
authors.forename: Zhejian
authors.initials: Z
authors.lastname: Wang
mesh_terms: D019969:Amphetamine-Related Disorders / Q000150:complications / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism; D019175:DNA Methylation / Q000187:drug effects; D044127:Epigenesis, Genetic / Q000187:drug effects*; D006801:Humans; D008297:Male; D008694:Methamphetamine / Q000633:toxicity*; D051783:Methyl-CpG-Binding Protein 2 / Q000378:metabolism; D010300:Parkinson Disease / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D051844:alpha-Synuclein / Q000235:genetics* / Q000378:metabolism
chemical_list: D016207:Cytokines; C497394:Mecp2 protein, rat; D051783:Methyl-CpG-Binding Protein 2; D012333:RNA, Messenger; C497606:Snca protein, rat; D051844:alpha-Synuclein; D008694:Methamphetamine; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases
keywords: DNA methylation; DNA methyltransferase 1; Methamphetamine; Methyl CpG binding protein 2; α-synuclein