期刊
NEUROBIOLOGY OF DISEASE
卷 29, 期 2, 页码 169-175出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2007.07.030
关键词
RNA; oxidative stress; Alzheimer's disease; mild cognitive impairment; lipid peroxidation
资金
- NIA NIH HHS [1P30-AG028383, P30 AG028383-02, P30 AG028383, P01 AG005119, 5-P01-AG05119, P01 AG005119-20A1] Funding Source: Medline
Studies show increased oxidative damage in the brains of subjects with Alzheimer's disease (AD) and mild cognitive impairment (MCI). To determine if RNA oxidation occurs in MCI, sections of hippocampus/parahippocampal gyros (HPG) from 5 MCI, 5 late stage AD (LAD) and 5 age-matched normal control (NC) subjects were subjected to immunohistochemistry using antibodies against 8-hydroxyguanine (8-OHG) and 1-N2-propanodeoxyguanosine (NPrG). Confocal microscopy showed 8-OHG and NPrG immunostaining was significantly (p<0.05) elevated in MCI and LAD HPG compared with NC subjects and was predominately associated with neurons identified using the MC-1 antibody that recognizes conformational alterations of tau, which are associated with early neurofibrillary tangle formation. Pretreating sections with RNase or DNase-I showed immunostaining for both adducts was primarily associated with RNA. to addition, levels of both adducts in MCI were comparable to those measured in LAD, suggesting RNA oxidation may be an early event in the pathogenesis of neuron degeneration in AD. (C) 2007 Elsevier Inc. All rights reserved.
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