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Mitochondrial Sirt3 Expression is Decreased in APP/PS1 Double Transgenic Mouse Model of Alzheimer’s Disease

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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.

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Acknowledgments

This study was supported by National Key Clinical Specialties Construction Program of China (No. [2013]544) and Application Program of Chongqing Science and Technology Commission, China (cstc2014yykfA110002).

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    Authors and Affiliations

    1. Department of Human Anatomy, Institute of Neuroscience, Chongqing Medical University, Chongqing, 400016, China

      Wenxiu Yang, Nan Zhao, Wei Liu & Weihua Yu

    2. Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China

      Yan Zou, Man Zhang, Qi Tian, Min Gu, Rui Shi & Yang Lü

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    1. Wenxiu Yang
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    2. Yan Zou
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    3. Man Zhang
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    Correspondence to Weihua Yu.

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    Wenxiu Yang and Yan Zou have contributed equally to this manuscript.

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    Yang, W., Zou, Y., Zhang, M. et al. Mitochondrial Sirt3 Expression is Decreased in APP/PS1 Double Transgenic Mouse Model of Alzheimer’s Disease. Neurochem Res 40, 1576–1582 (2015). https://doi.org/10.1007/s11064-015-1630-1

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    • DOI: https://doi.org/10.1007/s11064-015-1630-1

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