Mitochondrial SIRT3 In APP/PS1 Double Transgenic Mouse Of Alzheimer’s Disease

Purpose:Emerging data suggests that mitochondrial dysfunction is prominently involved in Alzheimer disease (AD) progression. Sirtuin-3 (Sirt3) is a member of the sirtuin family of nicotinamide adenine dinucleotide dependent deacetylases that regulates a variety of mitochondrial functions and suppresses mitochondria-related physiology. Here, we determined Sirt3 expression in a mouse model of AD.Methods:Spatial learning and memory were tested by Morris water maze in APP/PS1 double transgenic mice. The expression of Sirt3 was assayed by real-time quantitative PCR and western blotting. Age-and gender-matched wild-type (WT) littermates were used as controls. Cortical Sirt3 localization was assessed using immunohistochemistry.Results:The expression of Sirt3 mRNA was significantly lower in the cortex of APP/PS1 double transgenic mice than in WT littermates (0.83β 0.24 vs.1.10±0.21, P<0.05). A comparable reduction was found in Sirt3 protein levels using western blotting. The ratio of mean optical density (MOD) of total Sirt3/β-actin in the cortex was 0.77±.11 in APP/PS1 double transgenic mice and 1.34±0.17 in the WT littermates (P< 0.01). Immunohistochemistry showed the same change as western blotting. The ratio of MOD of integral optical density/total area in APP/PS1 and WT littermates was 0.58±0.02 and 0.71±0.05 (P< 0.01). These data showed that Sirt3 was depleted in APP/PS1 double transgenic mice.Conclusion:The results suggest that mitochondrial Sirt3 might participate in the development of AD via mitochondrial dysfunction.