Open AccessHDAC 3 negatively regulates spatial memory in a mouse model of Alzheimer's disease
Author(s) -
Zhu Xiaolei,
Wang Sulei,
Yu Linjie,
Jin Jiali,
Ye Xing,
Liu Yi,
Xu Yun
Publication year - 2017
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12642
Subject(s) - morris water navigation task , hdac3 , hippocampus , dendritic spine , microglia , hdac1 , presenilin , amyloid precursor protein , barnes maze , alzheimer's disease , neuroscience , biology , histone , endocrinology , medicine , microbiology and biotechnology , disease , histone deacetylase , hippocampal formation , biochemistry , spatial learning , inflammation , gene
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 .