Oxidatively modified nucleic acids in preclinical Alzheimer's disease (PCAD) brain

Autor: Mark A. Lovell, Melissa A. Bradley, Sony Soman
Rok vydání: 2011
Předmět:
Zdroj: Mechanisms of Ageing and Development. 132:443-448
ISSN: 0047-6374
DOI: 10.1016/j.mad.2011.08.003
Popis: Previous studies show increased oxidative DNA and RNA damage and diminished 8-oxoguanine glycosylase (OGG1) mediated base excision repair in vulnerable brain regions of mild cognitive impairment and late-stage Alzheimer's disease (LAD) subjects compared to normal control (NC) subjects. Recently, a preclinical stage of AD (PCAD) has been described in which subjects show no overt clinical manifestations of AD but demonstrate significant AD pathology at autopsy. To determine if DNA or RNA oxidation are significantly elevated in PCAD brain we quantified 8-hydroxyguanine (8-OHG) in sections of hippocampus/parahippocamapal gyri in PCAD and NC subjects using immunohistochemistry and confocal microscopy and in superior and middle temporal gyri (SMTG) using gas chromatography/mass spectrometry. To determine if increased DNA oxidation is associated with altered repair capacity, levels of OGG1 protein in HPG were measured by immunohistochemistry and levels of OGG1 mRNA were measured in SMTG using quantitative PCR. Results show significantly increased (p
Databáze: OpenAIRE