Oxidatively modified RNA in mild cognitive impairment.
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 gyrus (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. In 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.
Lovell
Mark A
MA
Department of Chemistry, University of Kentucky, Lexington, KY 40506, USA. malove2@uky.edu
Markesbery
William R
WR
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology; D000704:Analysis of Variance; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D027682:Cation Transport Proteins / Q000378:metabolism; D003072:Cognition Disorders / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000073840:Copper-Transporting ATPases; D003849:Deoxyguanosine / Q000378:metabolism; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives / Q000378:metabolism; D006801:Humans; D008297:Male; D018613:Microscopy, Confocal; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011180:Postmortem Changes; D012313:RNA / Q000378:metabolism*; D018709:Statistics, Nonparametric
D027682:Cation Transport Proteins; C024829:8-hydroxyguanine; D006147:Guanine; D012313:RNA; D000251:Adenosine Triphosphatases; C081184:ATP7A protein, human; D000073840:Copper-Transporting ATPases; D003849:Deoxyguanosine