Epigenetic regulation of brain region-specific microglia clearance activity

被引：326

作者：

Ayata, Pinar ^{[1
,2
]}

Badimon, Ana ^{[1
]}

Strasburger, Hayley J. ^{[1
]}

Duff, Mary Kaye ^{[1
]}

Montgomery, Sarah E. ^{[1
]}

Loh, Yong-Hwee E. ^{[1
]}

Ebert, Anja ^{[3
]}

Pimenova, Anna A. ^{[1
,2
]}

Ramirez, Brianna R. ^{[1
]}

Chan, Andrew T. ^{[1
]}

Sullivan, Josefa M. ^{[1
]}

Purushothaman, Immanuel ^{[1
]}

Scarpa, Joseph R. ^{[4
]}

Goate, Alison M. ^{[1
,2
,4
]}

Busslinger, Meinrad ^{[3
]}

Shen, Li ^{[1
]}

Losic, Bojan ^{[4
,5
]}

Schaefer, Anne ^{[1
,2
]}

机构：

[1] Icahn Sch Med Mt Sinai, Friedman Brain Inst, Dept Psychiat, Fishberg Dept Neurosci, New York, NY 10029 USA

[2] Icahn Sch Med Mt Sinai, Ronald M Loeb Ctr Alzheimers Dis, New York, NY 10029 USA

[3] Vienna Bioctr, Res Inst Mol Pathol, Vienna, Austria

[4] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA

[5] Icahn Sch Med Mt Sinai, Tisch Canc Inst, Canc Immunol Program, New York, NY 10029 USA

来源：

NATURE NEUROSCIENCE | 2018年 / 21卷 / 08期

基金：

美国国家卫生研究院;

关键词：

DIFFERENTIAL EXPRESSION ANALYSIS; TRANSLATIONAL PROFILING APPROACH; PURKINJE NEURONS; CELL; RECEPTORS; MOUSE; DEGENERATION; MACROPHAGES; DYNAMICS; PROTEIN;

D O I：

10.1038/s41593-018-0192-3

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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.

引用

页码：1049 / +

页数：18

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