| Literature DB >> 30038282 |
Pinar Ayata1,2, Ana Badimon1, Hayley J Strasburger1, Mary Kaye Duff1, Sarah E Montgomery1, Yong-Hwee E Loh1, Anja Ebert3, Anna A Pimenova1,2, Brianna R Ramirez1, Andrew T Chan1, Josefa M Sullivan1, Immanuel Purushothaman1, Joseph R Scarpa4, Alison M Goate1,2,4, Meinrad Busslinger3, Li Shen1, Bojan Losic4,5, Anne Schaefer6,7.
Abstract
The rapid elimination of dying neurons and nonfunctional synapses in the brain is carried out by microglia, the resident myeloid cells of the brain. Here we show that microglia clearance activity in the adult brain is regionally regulated and depends on the rate of neuronal attrition. Cerebellar, but not striatal or cortical, microglia exhibited high levels of basal clearance activity, which correlated with an elevated degree of cerebellar neuronal attrition. Exposing forebrain microglia to apoptotic cells activated gene-expression programs supporting clearance activity. We provide evidence that the polycomb repressive complex 2 (PRC2) epigenetically restricts the expression of genes that support clearance activity in striatal and cortical microglia. Loss of PRC2 leads to aberrant activation of a microglia clearance phenotype, which triggers changes in neuronal morphology and behavior. Our data highlight a key role of epigenetic mechanisms in preventing microglia-induced neuronal alterations that are frequently associated with neurodegenerative and psychiatric diseases.Entities:
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Year: 2018 PMID： 30038282 PMCID： PMC6090564 DOI： 10.1038/s41593-018-0192-3
Source DB: PubMed Journal: Nat Neurosci ISSN： 1097-6256 Impact factor: 24.884