Neuronal RNA oxidation is a prominent feature of dementia with Lewy bodies.
An 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.
Nunomura
Akihiko
A
Department of Psychiatry and Neurology, Asahikawa Medical College, Higashi 2-1-1-1, Midorigaoka, Asahikawa 078-8510, Japan. nuno@asahika-med.ac.jp
Chiba
Shigeru
S
Kosaka
Kenji
K
Takeda
Atsushi
A
Castellani
Rudy J
RJ
Smith
Mark A
MA
Perry
George
G
D000368:Aged; D000369:Aged, 80 and over; D001344:Autopsy; D003851:Deoxyribonucleases / Q000378:metabolism; D005260:Female; D006151:Guanosine / Q000031:analogs & derivatives* / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D020961:Lewy Body Disease / Q000378:metabolism*; D008297:Male; D012260:Ribonucleases / Q000378:metabolism; D013702:Temporal Lobe / Q000378:metabolism*
D006151:Guanosine; C046215:8-hydroxyguanosine; D003851:Deoxyribonucleases; D012260:Ribonucleases