Colony-Stimulating Factor 1 Receptor Signaling Is Necessary for Microglia Viability, Unmasking a Microglia Progenitor Cell in the Adult Brain

被引：1522

作者：

Elmore, Monica R. P. ^{[1
]}

Najafi, Allison R. ^{[1
]}

Koike, Maya A. ^{[1
]}

Dagher, Nabil N. ^{[1
]}

Spangenberg, Elizabeth E. ^{[1
]}

Rice, Rachel A. ^{[1
]}

Kitazawa, Masashi ^{[3
]}

Matusow, Bernice ^{[2
]}

Nguyen, Hoa ^{[2
]}

West, Brian L. ^{[2
]}

Green, Kim N. ^{[1
]}

机构：

[1] Univ Calif Irvine, Inst Memory Impairments & Neurol Disorders, Dept Neurobiol & Behav, Irvine, CA 92697 USA

[2] Plexxikon Inc, Berkeley, CA 94710 USA

[3] Univ Calif Merced, Dept Mol & Cell Biol, Merced, CA 95343 USA

来源：

NEURON | 2014年 / 82卷 / 02期

基金：

美国国家卫生研究院;

关键词：

KINASE INHIBITOR; LANGERHANS CELLS; A-BETA; EXPRESSION; GROWTH; FMS; DIFFERENTIATION; MAINTENANCE; DEFICIENCY; PRECURSORS;

D O I：

10.1016/j.neuron.2014.02.040

中图分类号：

Q189 [神经科学];

学科分类号：

071006 [神经生物学];

摘要：

The colony-stimulating factor 1 receptor (CSF1R) is a key regulator of myeloid lineage cells. Genetic loss of the CSF1R blocks the normal population of resident microglia in the brain that originates from the yolk sac during early development. However, the role of CSF1R signaling in microglial homeostasis in the adult brain is largely unknown. To this end, we tested the effects of selective CSF1R inhibitors on microglia in adult mice. Surprisingly, extensive treatment results in elimination of similar to 99% of all microglia brain-wide, showing that microglia in the adult brain are physiologically dependent upon CSF1R signaling. Mice depleted of microglia show no behavioral or cognitive abnormalities, revealing that microglia are not necessary for these tasks. Finally, we discovered that the microglia-depleted brain completely repopulates with new microglia within 1 week of inhibitor cessation. Microglial repopulation throughout the CNS occurs through proliferation of nestin-positive cells that then differentiate into microglia.

引用

页码：380 / 397

页数：18

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