Molecular studies on Abeta(42) induced genomic instability in aged rabbit brain

Neurochemistry International
Ramesh B NarasingappaRao Kosagisharaf Jagannatha

Abstract

DNA stability and conformation are important in the life cycle of an organism. The DNA instability is postulated to be one of the risk factors for neuronal death in neurodegenerative disorders. Among all other risk factors, amyloid is one of the most important risk factor for neurodegeneration. Abeta(42) is implicated in Alzheimer's disease (AD). Studies from our lab and elsewhere have shown that Abeta(42) could cause DNA damage and alter DNA stability in vitro and there are no mechanistic studies to understand Abeta induced genomic instability under in vivo condition. The present study aims to characterize Abeta(42) induced DNA instability and also to map the changes in DNA conformation in vivo and its correlation to brain structural changes. The aged (4yr) New Zealand rabbits are intracisternally injected with Abeta(42) and are sacrificed after 25 days, when the rabbits developed AD like behavior. Genomic DNA is isolated from frontal cortex (FC), hippocampus (H) and midbrain (M) regions of Abeta(42) injected and control rabbit brain. The DNA stability parameters are analyzed. And the results showed that DNA is damaged in FC and H; where as in M, DNA is in condensed state. The DNA conformation study evidenced the presence of C...Continue Reading

Citations

Jul 5, 2011·Neurochemistry International·B N RameshK S J Rao
Oct 1, 2015·Psychogeriatrics : the Official Journal of the Japanese Psychogeriatric Society·Obulesu MagisettyShamasundar N Mannar

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