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Olfactory Dysfunctions and Decreased Nitric Oxide Production in the Brain of Human P301L Tau Transgenic Mice

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Abstract

Different patterns of olfactory dysfunction have been found in both patients and mouse models of Alzheimer’s Disease. However, the underlying mechanism of the dysfunction remained unknown. Deficits of nitric oxide production in brain can cause olfactory dysfunction by preventing the formation of olfactory memory. The aim of this study was to investigate the behavioral changes in olfaction and alterations in metabolites of nitric oxide, nitrate/nitrite concentration, in the brain of human P301L tau transgenic mice. The tau mice showed impairments in olfaction and increased abnormal phosphorylation of Tau protein at AT8 in different brain areas, especially in olfactory bulb. We now report that these olfactory deficits and Tau pathological changes were accompanied by decreased nitrate/nitrite concentration in the brain, especially in the olfactory bulb, and reduced expression of nNOS in the brain of tau mice. These findings provided evidence of olfactory dysfunctions correlated with decreased nitric oxide production in the brain of tau mice.

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Acknowledgments

Human tau (htau) expression plasmid pR5 was kindly provided by Dr. Jürgen Götz. This study was supported by the China Medical Board (Grant No. 98-677).

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Authors and Affiliations

  1. Department of Pharmacology, Zhongshan School of Medicine, Sun-Yet Sen University, Zhongshan 2nd Rd., Guangzhou, 510080, China

    Yang Hu, Wenting Ding, Xiaonan Zhu, Ruzhu Chen & Xuelan Wang

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  1. Yang Hu
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  2. Wenting Ding
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  3. Xiaonan Zhu
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  4. Ruzhu Chen
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  5. Xuelan Wang
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Correspondence to Xuelan Wang.

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Hu, Y., Ding, W., Zhu, X. et al. Olfactory Dysfunctions and Decreased Nitric Oxide Production in the Brain of Human P301L Tau Transgenic Mice. Neurochem Res 41, 722–730 (2016). https://doi.org/10.1007/s11064-015-1741-8

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  • DOI: https://doi.org/10.1007/s11064-015-1741-8

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