title: Dysfunction of mitochondrial dynamics in the brains of scrapie-infected mice.
abstract: Mitochondrial dysfunction is a common and prominent feature of many neurodegenerative diseases, including prion diseases; it is induced by oxidative stress in scrapie-infected animal models. In previous studies, we found swelling and dysfunction of mitochondria in the brains of scrapie-infected mice compared to brains of controls, but the mechanisms underlying mitochondrial dysfunction remain unclear. To examine whether the dysregulation of mitochondrial proteins is related to the mitochondrial dysfunction associated with prion disease, we investigated the expression patterns of mitochondrial fusion and fission proteins in the brains of ME7 prion-infected mice. Immunoblot analysis revealed that Mfn1 was up-regulated in both whole brain and specific brain regions, including the cerebral cortex and hippocampus, of ME7-infected mice compared to controls. Additionally, expression levels of Fis1 and Mfn2 were elevated in the hippocampus and the striatum, respectively, of the ME7-infected brain. In contrast, Dlp1 expression was significantly reduced in the hippocampus in the ME7-infected brain, particularly in the cytosolic fraction. Finally, we observed abnormal mitochondrial enlargement and histopathological change in the hippocampus of the ME7-infected brain. These observations suggest that the mitochondrial dysfunction, which is presumably caused by the dysregulation of mitochondrial fusion and fission proteins, may contribute to the neuropathological changes associated with prion disease.
authors.affiliation: Department of Microbiology, College of Medicine, Hallym University, 1 Okcheon-dong, Chuncheon, Gangwon-do 200-702, Republic of Korea; Ilsong Institute of Life Science, Hallym University, 1605-4 Gwanyang-dong, Dongan-gu, Anyang, Gyeonggi-do 431-060, Republic of Korea.
authors.forename: Hong-Seok
authors.initials: HS
authors.lastname: Choi
authors.affiliation: Ilsong Institute of Life Science, Hallym University, 1605-4 Gwanyang-dong, Dongan-gu, Anyang, Gyeonggi-do 431-060, Republic of Korea.
authors.forename: Yeong-Gon
authors.initials: YG
authors.lastname: Choi
authors.affiliation: Ilsong Institute of Life Science, Hallym University, 1605-4 Gwanyang-dong, Dongan-gu, Anyang, Gyeonggi-do 431-060, Republic of Korea.
authors.forename: Hae-Young
authors.initials: HY
authors.lastname: Shin
authors.affiliation: Ilsong Institute of Life Science, Hallym University, 1605-4 Gwanyang-dong, Dongan-gu, Anyang, Gyeonggi-do 431-060, Republic of Korea.
authors.forename: Jae-Min
authors.initials: JM
authors.lastname: Oh
authors.affiliation: Department of Microbiology, College of Medicine, Hallym University, 1 Okcheon-dong, Chuncheon, Gangwon-do 200-702, Republic of Korea; Ilsong Institute of Life Science, Hallym University, 1605-4 Gwanyang-dong, Dongan-gu, Anyang, Gyeonggi-do 431-060, Republic of Korea.
authors.forename: Jeong-Ho
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Food Science and Nutrition, Pukyong National University, 599-1 Daeyeon-3-dong, Nam-gu, Busan 608-737, Republic of Korea.
authors.forename: Jae-Il
authors.initials: JI
authors.lastname: Kim
authors.affiliation: New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314, USA.
authors.forename: Richard I
authors.initials: RI
authors.lastname: Carp
authors.affiliation: Ilsong Institute of Life Science, Hallym University, 1605-4 Gwanyang-dong, Dongan-gu, Anyang, Gyeonggi-do 431-060, Republic of Korea. Electronic address: ekchoi@hallym.ac.kr.
authors.forename: Eun-Kyoung
authors.initials: EK
authors.lastname: Choi
authors.affiliation: Department of Microbiology, College of Medicine, Hallym University, 1 Okcheon-dong, Chuncheon, Gangwon-do 200-702, Republic of Korea; Ilsong Institute of Life Science, Hallym University, 1605-4 Gwanyang-dong, Dongan-gu, Anyang, Gyeonggi-do 431-060, Republic of Korea. Electronic address: yskim@hallym.ac.kr.
authors.forename: Yong-Sun
authors.initials: YS
authors.lastname: Kim
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D003600:Cytosol / Q000378:metabolism; D004195:Disease Models, Animal; D034281:Dynamins / Q000378:metabolism; D020558:GTP Phosphohydrolases; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology*; D063154:Mitochondrial Dynamics; D024101:Mitochondrial Proteins / Q000378:metabolism; D018620:PrPSc Proteins / Q000378:metabolism; D012608:Scrapie / Q000378:metabolism / Q000473:pathology*
chemical_list: C561064:FIS1 protein, mouse; D024101:Mitochondrial Proteins; D018620:PrPSc Proteins; D020558:GTP Phosphohydrolases; C488750:Mfn1 protein, mouse; C488751:Mfn2 protein, mouse; C486391:Dnm1l protein, mouse; D034281:Dynamins
keywords: Fission; Mitochondrial dysfunction; Mitochondrial fusion; Prion disease; Scrapie