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HDAC3 negatively regulates spatial memory in a mouse model of Alzheimer's disease
- Source :
- Aging Cell
- Publication Year :
- 2017
- Publisher :
- Wiley, 2017.
-
Abstract
- Summary The accumulation and deposition of beta‐amyloid (Aβ) is a key neuropathological hallmark of Alzheimer's disease (AD). Histone deacetylases (HDACs) 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 HDAC3 in the pathogenesis of AD. Nuclear HDAC3 is significantly increased in the hippocampus of 6‐ and 9‐month‐old APPswe/PS1dE9 (APP/PS1) mice compared with that in age‐matched wild‐type C57BL/6 (B6) mice. Lentivirus ‐mediated inhibition or overexpression of HDAC3 was used in the hippocampus of APP/PS1 mice to investigate the role of HDAC3 in spatial memory, amyloid burden, dendritic spine density, glial activation and tau phosphorylation. Inhibition of HDAC3 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/PS1 mice. Dendritic spine density is increased, while microglial activation is alleviated after HDAC3 inhibition in the hippocampus of 9‐month‐old APP/PS1 mice. Furthermore, HDAC3 overexpression in the hippocampus increases Aβ levels, activates microglia, and decreases dendritic spine density in 6‐month‐old APP/PS1 mice. In conclusion, our results indicate that HDAC3 negatively regulates spatial memory in APP/PS1 mice and HDAC3 inhibition might represent a potential therapy for the treatment of AD.
- Subjects :
- 0301 basic medicine
Aging
Dendritic spine
Hippocampus
Morris water navigation task
Plaque, Amyloid
Phenylenediamines
Pathogenesis
Mice
0302 clinical medicine
Phosphorylation
biology
Microglia
Alzheimer's disease
spatial memory
Histone
medicine.anatomical_structure
Original Article
histone deacetylase3
Gene isoform
medicine.medical_specialty
Dendritic Spines
Genetic Vectors
Mice, Transgenic
tau Proteins
Histone Deacetylases
03 medical and health sciences
Alzheimer Disease
Internal medicine
mental disorders
medicine
Animals
Humans
Maze Learning
beta‐amyloid
Cell Nucleus
Acrylamides
Amyloid beta-Peptides
Lentivirus
Original Articles
Cell Biology
HDAC3
Histone Deacetylase Inhibitors
Mice, Inbred C57BL
Disease Models, Animal
030104 developmental biology
Endocrinology
Gene Expression Regulation
nervous system
Immunology
biology.protein
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 14749718
- Volume :
- 16
- Database :
- OpenAIRE
- Journal :
- Aging Cell
- Accession number :
- edsair.doi.dedup.....08c9eac2eee56c477a870e773de3feb5