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Cited by 165Neuroscience and Neuropharmacology ResearchNeuroinflammation and Neurodegeneration MechanismsCholesterol and Lipid Metabolism

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Astrocytic ApoE reprograms neuronal cholesterol metabolism and histone-acetylation-mediated memory

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Li, Xiaohui, Zhang, Juan, Li, Dingfeng, He, Cheng, He, Keqiang, Xue, Tian, Wan, Lili, Zhang, Chi, Liu, Qiang·2021·Neuron
DOI 10.1016/j.neuron.2021.01.005
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Abstract

Astrocytes metabolically interact with neighboring neurons by providing multiple substances to neurons. How astrocytes regulate neural functions via altering the neuronal metabolic state remains elusive. Here, we demonstrate that astrocytic ApoE vectors a variety of microRNAs (miRNAs), and these miRNAs specifically silence genes involved in neuronal cholesterol biosynthesis, ultimately accounting for accumulation of the pathway-initiating substrate acetyl-CoA. Consequently, histone acetylation is promoted, and transcription is activated in neurons. Functionally, we demonstrate that ApoE-mediated neuronal histone acetylation leads to increased H3K27ac enrichment in the promoters of multiple neuronal immediate early genes and subsequently to enhanced memory consolidation in mice. Importantly, human ApoE4 vectors lower levels of miRNAs than ApoE3 and therefore is less capable of metabolic and epigenetic regulation in neurons. Collectively, our findings define an astrocytic ApoE-mediated neuronal epigenetic mechanism as a novel means through which astrocytes modulate brain connectivity and function.

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Metadata

Authors
Li, X., Zhang, J., Li, D., He, C., He, K., Xue, T., Wan, L., Zhang, C., & Liu, Q.
Affiliations
  • University of Science and Technology of China (CN)
  • University of Pennsylvania (US)
  • Harvard University (US)
Corresponding author
  • Zhang, Juan
  • Liu, Qiang
ORCID
Venue
Neuron
Publisher
Elsevier BV
Published
2021-03
Volume
109
Issue
6
Pages
957-970.e8
ISSN
0896-6273 (ISSN-L)
DOI
10.1016/j.neuron.2021.01.005
OpenAlex
W3124009158
Cited by
165
References
0
Citations by year
2026: 28 · 2025: 32 · 2024: 35 · 2023: 29 · 2022: 30 · 2021: 11
FWCI
12.09
Type
journal article
Language
en
Open access
Licence
Locations
  • Neuron (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Key Research and Development Program of China (2020YFA0509300)
  • Fundamental Research Funds for the Central Universities
  • Innovative Program of Development Foundation of Hefei Center for Physical Science and Technology (2018CXFX005)
  • National Natural Science Foundation of China (31871082, 82071185, 91849101)
  • Natural Science Foundation of Anhui Province (2008085QC117)
  • Chinese Academy of Sciences (QYZDB-SSW-SMC035, XDB39000000)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
Keywords
astrocytes, apolipoprotein E, microRNA transfer, histone acetylation, H3K27ac, memory consolidation, epigenetic regulation, acetyl-CoA, APOE ε4, APOE3, immediate early genes, astrocyte-neuron metabolic coupling
MeSH terms
Memory Consolidation, Acetylation, Animals, Apolipoproteins E, Astrocytes, Cell Line, Cholesterol, Gene Expression Regulation, Histones, Humans, Mice, Inbred C57BL, Neurons, Epigenesis, Genetic, Mice

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