HDAC 3 negatively regulates spatial memory in a mouse model of Alzheimer's disease
Open accessAbstract
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.
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Inhibition of HDAC3 in hippocampal tissue reduced amyloid plaque load and Aβ levels and attenuated microglia activation in the brains of APP/PS1 mice.
“inhibition of HDAC3 in the hippocampal tissue reduced amyloid plaque load and Aβ levels and attenuated microglia activation in the brains of APP/PS1 mice [143].”
From Beneficial Effects of Spirulina Consumption on Brain Health (2022) · cites this paper as [143]
In the hippocampus of 6- and 9-month-old APP/PS1 mice, HDAC3 does not affect the levels of phosphorylated Tau protein.
“in the hippocampus of 6- and 9-month-old APP/PS1 mice, HDAC3 does not affect the levels of phosphorylated Tau protein.”
From Beneficial Effects of Spirulina Consumption on Brain Health (2022) · cites this paper as [143]
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Retracted
- Authors
- Zhu, X., Wang, S., Yu, L., Jin, J., Ye, X., Liu, Y., & Xu, Y.
- Affiliations
- Nanjing Brain Hospital (CN)
- Nanjing Traditional Chinese Medicine Hospital (CN)
- Nanjing Drum Tower Hospital (CN)
- Corresponding author
- Xu, Yun
- Venue
- Aging Cell
- Publisher
- Wiley
- Published
- 2017-08-03
- Volume
- 16
- Issue
- 5
- Pages
- 1073-1082
- ISSN
- 1474-9718 (ISSN-L)
- 1474-9726
- PMC
- PMC5595690
- OpenAlex
- W2744186560
- Cited by
- 112
- References
- 44
- Citations by year
- 2026: 11 · 2025: 15 · 2024: 14 · 2023: 22 · 2022: 12 · 2021: 7 · 2020: 13 · 2019: 8 · 2018: 10
- FWCI
- 6.27
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Aging Cell (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81200839, 81671055, 81300988, 81230026, 81630028, 81171085)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- HDAC3, Alzheimer's disease, spatial memory, amyloid-beta, APP/PS1 mice, hippocampus, dendritic spine density, microglial activation, tau phosphorylation, HDAC3 inhibition, cognitive impairment
- MeSH terms
- Histone Deacetylase 3, Acrylamides, Alzheimer Disease, Animals, Cell Nucleus, Disease Models, Animal, Gene Expression Regulation, Genetic Vectors, Hippocampus, Histone Deacetylases, Humans, Mice, Inbred C57BL, Mice, Transgenic, Phenylenediamines, Phosphorylation, Lentivirus, Amyloid beta-Peptides, tau Proteins, Maze Learning, Dendritic Spines, Mice, Histone Deacetylase Inhibitors, Plaque, Amyloid
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