title: Mitochondrial Sirt3 Expression is Decreased in APP/PS1 Double Transgenic Mouse Model of Alzheimer's Disease.
abstract: 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. 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. The expression of sirt3 mRNA was significantly lower in the cortex of APP/PS1 double transgenic mice than in WT littermates (0.83 ± 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 ± 0.11 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 show that sirt3 was depleted in APP/PS1 double transgenic mice. The results suggest that mitochondrial sirt3 might participate in the development of AD via mitochondrial dysfunction.
authors.affiliation: Department of Human Anatomy, Institute of Neuroscience, Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Wenxiu
authors.initials: W
authors.lastname: Yang
authors.forename: Yan
authors.initials: Y
authors.lastname: Zou
authors.forename: Man
authors.initials: M
authors.lastname: Zhang
authors.forename: Nan
authors.initials: N
authors.lastname: Zhao
authors.forename: Qi
authors.initials: Q
authors.lastname: Tian
authors.forename: Min
authors.initials: M
authors.lastname: Gu
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Rui
authors.initials: R
authors.lastname: Shi
authors.forename: Yang
authors.initials: Y
authors.lastname: Lü
authors.forename: Weihua
authors.initials: W
authors.lastname: Yu
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D053764:Presenilin-1 / Q000235:genetics; D056566:Sirtuin 3 / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D016564:Amyloid beta-Protein Precursor; D053764:Presenilin-1; C525046:Sirt3 protein, mouse; D056566:Sirtuin 3