Cited by 207Neuroinflammation and Neurodegeneration MechanismsHistone Deacetylase Inhibitors ResearchNeurogenesis and neuroplasticity mechanisms

The DOI matches its Crossref record; 55 of the 55 references it cites were found in a registry or an index.

Histone Deacetylases 1 and 2 Regulate Microglia Function during Development, Homeostasis, and Neurodegeneration in a Context-Dependent Manner

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Abstract

Microglia as tissue macrophages contribute to the defense and maintenance of central nervous system (CNS) homeostasis. Little is known about the epigenetic signals controlling microglia function in vivo. We employed constitutive and inducible mutagenesis in microglia to delete two class I histone deacetylases, Hdac1 and Hdac2. Prenatal ablation of Hdac1 and Hdac2 impaired microglial development. Mechanistically, the promoters of pro-apoptotic and cell cycle genes were hyperacetylated in absence of Hdac1 and Hdac2, leading to increased apoptosis and reduced survival. In contrast, Hdac1 and Hdac2 were not required for adult microglia survival during homeostasis. In a mouse model of Alzheimer's disease, deletion of Hdac1 and Hdac2 in microglia, but not in neuroectodermal cells, resulted in a decrease in amyloid load and improved cognitive impairment by enhancing microglial amyloid phagocytosis. Collectively, we report a role for epigenetic factors that differentially affect microglia development, homeostasis, and disease that could potentially be utilized therapeutically.

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Crossref · 10.1016/j.immuni.2018.02.016

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  1. Hagelkruys, 2014, A single allele of Hdac2 but not Hdac1 is sufficient for normal mouse brain development in the absence of its paralog, Development, 141, 604, 10.1242/dev.100487 · DOI · Paper page

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Metadata

Authors
Datta, M., Staszewski, O., Raschi, E., Frosch, M., Hagemeyer, N., Tay, T. L., Blank, T., Kreutzfeldt, M., Merkler, D., Ziegler-Waldkirch, S., Matthias, P., Meyer-Luehmann, M., & Prinz, M.
Affiliations
  • University of Freiburg (DE)
  • University of Bologna (IT)
  • University of Geneva (CH)
  • Friedrich Miescher Institute (CH)
Corresponding author
  • Datta, Moumita
  • Prinz, Marco
Venue
Immunity
Publisher
Elsevier BV
Published
2018-03
Volume
48
Issue
3
Pages
514-529.e6
ISSN
1074-7613 (ISSN-L)
OpenAlex
W2789949980
Cited by
206
References
55
Citations by year
2026: 14 · 2025: 22 · 2024: 32 · 2023: 21 · 2022: 14 · 2021: 29 · 2020: 34 · 2019: 24 · 2018: 16
FWCI
11.55
Type
journal article
Language
en
Open access
Locations
  • Immunity (publishedVersion)
  • PubMed (publishedVersion)
  • Archive ouverte UNIGE (University of Geneva) (publishedVersion)
  • Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
Funders
  • BMBF-funded competence network of multiple sclerosis (KKNMS) (01GI1303B)
  • Sobek-Foundation
  • DFG (SFB 992, SFB1160, SFB/TRR167)
  • Ministry of Science, Research and Arts, Baden-Wuerttemberg
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Keywords
microglia, histone deacetylase, HDAC1, HDAC2, epigenetic regulation, microglial development, microglial homeostasis, neurodegeneration, Alzheimer's disease, microglial apoptosis, cognitive impairment, CNS homeostasis
MeSH terms
Animals, Disease Models, Animal, Gene Expression Regulation, Histones, Homeostasis, Memory Disorders, Mice, Transgenic, Phagocytosis, Gene Expression, Apoptosis, Microglia, Mice, Knockout, Neurodegenerative Diseases, Gene Expression Profiling, Epigenesis, Genetic, Cell Proliferation, Mice, Neurogenesis, Histone Deacetylase 1, Histone Deacetylase 2, Plaque, Amyloid, Transcriptome, Spatial Learning

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