title: Aberrant Alterations of Mitochondrial Factors Drp1 and Opa1 in the Brains of Scrapie Experiment Rodents.
abstract: The abnormal mitochondrial dynamics has been reported in the brains of some neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD), but limitedly described in prion disease. Dynamin-related protein 1 (Drpl) and optic atrophy protein 1 (Opa1) are two essential elements for mitochondria fission and fusion. To evaluate possible changes of mitochondria dynamics during prion infection, the situations of brain Drp1 and Opa1 of scrapie strains 139A, ME7, and S15 mice, as well as 263K-infected hamsters, were analyzed. Significant decreases of brain Drp1 were observed in scrapie-infected rodents at terminal stage by Western blots and immunohistochemical assays, while the levels of Opa1 also showed declined tendency in the brains of scrapie-infected rodents. Immunofluorescent assays illustrated well localization of Drp1 or Opa1 within NeuN-positive cells. Moreover, the S-nitrosylated forms of Drp1significantly increased in the brain tissues of 139A- and ME7-infected mice at terminal stage. Dynamic analysis of Drp1 and SNO-Dpr1 in the brains collected at different time points within the incubation period of 139A-infected mice demonstrated that the whole Drp1 decreased at all tested samples, whereas the SNO-Drp1 remarkably increased in the sample of 90-day post-infection (dpi), reached to the peak in that of 120 dpi and dropped down but still maintained at higher level at the end of disease. The levels of apoptotic factors cleaved caspase 9, caspase 3, and Bax were also markedly increased in the brain tissues of the mice infected with agents 139A and ME7. Our data indicate a disorder of mitochondria dynamics in the brains of prion infection, largely depending on the abnormal alteration of brain Drp1.
authors.affiliation: State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, China.|Chinese Center for Disease Control and Prevention, National Institute for Viral Disease Control and Prevention, Chang-Bai Rd 155, Beijing, 102206, China.
authors.forename: Xiao -Dong
authors.initials: X-
authors.lastname: Yang
authors.affiliation: State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, China. shiqi76@126.com.|Chinese Center for Disease Control and Prevention, National Institute for Viral Disease Control and Prevention, Chang-Bai Rd 155, Beijing, 102206, China. shiqi76@126.com.
authors.forename: Qi
authors.initials: Q
authors.lastname: Shi
authors.affiliation: State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, China.|Chinese Center for Disease Control and Prevention, National Institute for Viral Disease Control and Prevention, Chang-Bai Rd 155, Beijing, 102206, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Sun
authors.affiliation: State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, China.|Chinese Center for Disease Control and Prevention, National Institute for Viral Disease Control and Prevention, Chang-Bai Rd 155, Beijing, 102206, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Lv
authors.affiliation: State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, China.|Chinese Center for Disease Control and Prevention, National Institute for Viral Disease Control and Prevention, Chang-Bai Rd 155, Beijing, 102206, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Ma
authors.affiliation: State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, China.|Chinese Center for Disease Control and Prevention, National Institute for Viral Disease Control and Prevention, Chang-Bai Rd 155, Beijing, 102206, China.
authors.forename: Cao
authors.initials: C
authors.lastname: Chen
authors.affiliation: State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, China.|Chinese Center for Disease Control and Prevention, National Institute for Viral Disease Control and Prevention, Chang-Bai Rd 155, Beijing, 102206, China.
authors.forename: Kang
authors.initials: K
authors.lastname: Xiao
authors.affiliation: State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, China.|Chinese Center for Disease Control and Prevention, National Institute for Viral Disease Control and Prevention, Chang-Bai Rd 155, Beijing, 102206, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.affiliation: State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, China. dongxp238@sina.com.|Chinese Center for Disease Control and Prevention, National Institute for Viral Disease Control and Prevention, Chang-Bai Rd 155, Beijing, 102206, China. dongxp238@sina.com.|Chinese Academy of Sciences Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China. dongxp238@sina.com.
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Dong
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D020169:Caspases / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D034281:Dynamins / Q000378:metabolism*; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D063154:Mitochondrial Dynamics; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D012608:Scrapie / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D051028:bcl-2-Associated X Protein; D020169:Caspases; D020558:GTP Phosphohydrolases; C498809:Opa1 protein, mouse; C486391:Dnm1l protein, mouse; D034281:Dynamins
keywords: Apoptosis; Drp1; Mitochondria dynamics; Opa1; Scrapie