P4-108: Beta-amyloid reduces the expression of antioxidant repair genes

Although the mechanisms that lead to neurodegeneration in Alzheimer's disease (AD) are not clearly understood, there is evidence that beta amyloid (Aβ) can damage neurons by mechanisms that involve oxidative stress (OS) contributing to the onset and progression of AD.In the present study we analyze the change in the expression of OS repair genes SOD1 (superoxide dismutase 1), OGG (8-oxoguanine DNA glycosylase) and MAOA (monoamine oxidase A) over the medial and lateral septum after Aβ exposure at hippocampal CA1. To analyze the acute and chronic effect (AE and CE respectively) of Aβ, 12 adult male Sprague Dawley rats (300–350 g; Harlan) were used in this study, seven rats treated with the reverse peptide (Aβ 40–1) as control animals and five rats treated with the synthetic Aβ peptide 1–40. Compounds were administered by unilateral microinjection into the CA1 region of the hippocampus and rats were sacrificed 24 hours (AE) and 1 month (CE) after the event. RNA was isolated from the medial and lateral septum for posterior analysis by real-time quantitative PCR (rtqPCR). Changes in gene expression were reported in percentage relative to controls. Data were analyzed by one-way analysis of variance (ANOVA). Our results show that the acute effect of Aβ administration leads to a down regulation SOD1, OGG and MAOA genes in the medial septum with a reduced expression of 9%, 51% and 21% respectively when comparing their relative quantification (RQ) index versus the control group. In contrast, the three analyzed genes showed a tendency to over expression in the lateral septum, but without statistical significance. However, after one month of the Aβ administration, a decreased expression of the three genes was observed in the lateral septum (reduced by 74%, 38% and 27% respectively). SOD1 and MAOA genes were overexpressed and only the OGG gene maintain lower levels of expression (reduced by 61%) in the medial septum. We show that Aβ administration into the hippocampus interferes with the expression of the analyzed genes, suggesting that this interference can be an early manifestation in AD.