Neuronal RNA oxidation is a prominent feature of dementia with Lewy bodies

被引:67
作者
Nunomura, A
Chiba, S
Kosaka, K
Takeda, A
Castellani, RJ
Smith, MA
Perry, G
机构
[1] Asahikawa Med Coll, Dept Psychiat & Neurol, Asahikawa, Hokkaido 0788510, Japan
[2] Yokohama City Univ, Sch Med, Dept Psychiat, Yokohama, Kanagawa 2360004, Japan
[3] Tohoku Univ, Sch Med, Dept Neurol, Sendai, Miyagi 9808575, Japan
[4] Case Western Reserve Univ, Inst Pathol, Cleveland, OH 44106 USA
关键词
dementia with Lewy bodies; 8-hydroxyguanosine; oxidative stress; RNA; synucleinopathy;
D O I
10.1097/00001756-200211150-00009
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
An in situ approach was used to identify the oxidized nucleoside, 8-hydroxyguanosine in brains of dementia with Lewy bodies. Neurons with marked immunoreaction of 8-hydroxyguanosine in the cytoplasm were widely distributed in the hippocampal region and temporal neocortex. Relative intensity measurements of neuronal 8-hydroxyguanosine immunoreactivity showed that there was a significant increase in nucleic acid oxidation in dementia with Lewy bodies compared with controls. Treatment with nuclease (DNase or RNase) before the immunostaining demonstrated that RNA was a major site of nucleic acid oxidation. Together with the previously reported RNA oxidation in vulnerable neurons in Alzheimer and Parkinson diseases, neuronal RNA oxidation in dementia with Lewy bodies might represent one of the fundamental abnormalities in age-associated neurodegenerative diseases.
引用
收藏
页码:2035 / 2039
页数:5
相关论文
共 25 条
[1]   Chronic systemic pesticide exposure reproduces features of Parkinson's disease [J].
Betarbet, R ;
Sherer, TB ;
MacKenzie, G ;
Garcia-Osuna, M ;
Panov, AV ;
Greenamyre, JT .
NATURE NEUROSCIENCE, 2000, 3 (12) :1301-1306
[2]   Glycoxidation and oxidative stress in Parkinson disease and diffuse Lewy body disease [J].
Castellani, R ;
Smith, MA ;
Richey, PL ;
Perry, G .
BRAIN RESEARCH, 1996, 737 (1-2) :195-200
[3]  
CASTETELLANI RJ, 2000, NEUROSCI LETT, V319, P25
[4]   STABILITY OF CELL-SIZE AND NUCLEOLAR SIZE IN LEWY BODY CONTAINING NEURONS OF SUBSTANTIA-NIGRA IN PARKINSONS-DISEASE [J].
GERTZ, HJ ;
SIEGERS, A ;
KUCHINKE, J .
BRAIN RESEARCH, 1994, 637 (1-2) :339-341
[5]   Oxidative damage linked to neurodegeneration by selective α-synuclein nitration in synucleinopathy lesions [J].
Giasson, BI ;
Duda, JE ;
Murray, IVJ ;
Chen, QP ;
Souza, JM ;
Hurtig, HI ;
Ischiropoulos, H ;
Trojanowski, JQ ;
Lee, VMY .
SCIENCE, 2000, 290 (5493) :985-989
[6]   RNA sequestration to pathological lesions of neurodegenerative diseases [J].
Ginsberg, SD ;
Galvin, JE ;
Chiu, TS ;
Lee, VMY ;
Masliah, E ;
Trojanowski, JQ .
ACTA NEUROPATHOLOGICA, 1998, 96 (05) :487-494
[7]   NEUROPATHOLOGY OF IMMUNOHISTOCHEMICALLY IDENTIFIED BRAIN-STEM NEURONS IN PARKINSONS-DISEASE [J].
HALLIDAY, GM ;
LI, YW ;
BLUMBERGS, PC ;
JOH, TH ;
COTTON, RGH ;
HOWE, PRC ;
BLESSING, WW ;
GEFFEN, LB .
ANNALS OF NEUROLOGY, 1990, 27 (04) :373-385
[8]   Oxidative stress induces amyloid-like aggregate formation of NACP/α-synuclein in vitro [J].
Hashimoto, M ;
Hsu, LJ ;
Xia, Y ;
Takeda, A ;
Sisk, A ;
Sundsmo, M ;
Masliah, E .
NEUROREPORT, 1999, 10 (04) :717-721
[9]   α-synuclein protects against oxidative stress via inactivation of the c-Jun N-terminal kinase stress-signaling pathway in neuronal cells [J].
Hashimoto, M ;
Hsu, LJ ;
Rockenstein, E ;
Takenouchi, T ;
Mallory, M ;
Masliah, E .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (13) :11465-11472
[10]  
Jenner P, 1998, MOVEMENT DISORD, V13, P24