莫里斯水上航行任务
HDAC3型
海马体
树突棘
小胶质细胞
HDAC1型
早老素
淀粉样前体蛋白
巴恩斯迷宫
阿尔茨海默病
神经科学
生物
组蛋白
内分泌学
内科学
细胞生物学
医学
疾病
组蛋白脱乙酰基酶
海马结构
生物化学
空间学习
炎症
基因
作者
Xiaolei Zhu,Sulei Wang,Linjie Yu,Jiali Jin,Xing Ye,Yi Liu,Yun Xu
出处
期刊:Aging Cell
[Wiley]
日期:2017-08-03
卷期号:16 (5): 1073-1082
被引量:91
摘要
Summary The accumulation and deposition of beta‐amyloid (Aβ) is a key neuropathological hallmark of Alzheimer's disease ( AD ). Histone deacetylases ( HDAC s) are promising therapeutic targets for the treatment of AD , while the specific HDAC isoforms associated with cognitive improvement are poorly understood. In this study, we investigate the role of HDAC 3 in the pathogenesis of AD . Nuclear HDAC 3 is significantly increased in the hippocampus of 6‐ and 9‐month‐old APP swe/ PS 1dE9 ( APP / PS 1) mice compared with that in age‐matched wild‐type C57 BL /6 (B6) mice. Lentivirus ‐mediated inhibition or overexpression of HDAC3 was used in the hippocampus of APP/PS1 mice to investigate the role of HDAC 3 in spatial memory, amyloid burden, dendritic spine density, glial activation and tau phosphorylation. Inhibition of HDAC 3 in the hippocampus attenuates spatial memory deficits, as indicated in the Morris water maze test, and decreases amyloid plaque load and Aβ levels in the brains of APP / PS 1 mice. Dendritic spine density is increased, while microglial activation is alleviated after HDAC 3 inhibition in the hippocampus of 9‐month‐old APP / PS 1 mice. Furthermore, HDAC 3 overexpression in the hippocampus increases Aβ levels, activates microglia, and decreases dendritic spine density in 6‐month‐old APP / PS 1 mice. In conclusion, our results indicate that HDAC 3 negatively regulates spatial memory in APP / PS 1 mice and HDAC 3 inhibition might represent a potential therapy for the treatment of AD .
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