Olfactory Dysfunctions and Decreased Nitric Oxide Production in the Brain of Human P301L Tau Transgenic Mice.
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.
Department of Pharmacology, Zhongshan School of Medicine, Sun-Yet Sen University, Zhongshan 2nd Rd., Guangzhou, 510080, China.
Yang
Y
Hu
Department of Pharmacology, Zhongshan School of Medicine, Sun-Yet Sen University, Zhongshan 2nd Rd., Guangzhou, 510080, China.
Wenting
W
Ding
Department of Pharmacology, Zhongshan School of Medicine, Sun-Yet Sen University, Zhongshan 2nd Rd., Guangzhou, 510080, China.
Xiaonan
X
Zhu
Department of Pharmacology, Zhongshan School of Medicine, Sun-Yet Sen University, Zhongshan 2nd Rd., Guangzhou, 510080, China.
Ruzhu
R
Chen
Department of Pharmacology, Zhongshan School of Medicine, Sun-Yet Sen University, Zhongshan 2nd Rd., Guangzhou, 510080, China. mdswxl@mail.sysu.edu.cn.
Xuelan
X
Wang
D000818:Animals; D001921:Brain / Q000378:metabolism*; D004192:Discrimination, Psychological; D006801:Humans; D018782:Maze Learning; D008822:Mice, Transgenic; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis*; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D009830:Olfactory Bulb / Q000378:metabolism; D010766:Phosphorylation; D012903:Smell; D065852:Spatial Memory; D016875:tau Proteins / Q000235:genetics*
C054369:MAPT protein, human; D009566:Nitrates; D009573:Nitrites; D016875:tau Proteins; D009569:Nitric Oxide; D052248:Nitric Oxide Synthase Type I
Nitric oxide; Olfactory dysfunction; Tau; Transgenic mouse