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Neuron. 2014 Apr 16;82(2):380-97. doi: 10.1016/j.neuron.2014.02.040.

Colony-stimulating factor 1 receptor signaling is necessary for microglia viability, unmasking a microglia progenitor cell in the adult brain.

Author information

1
Department of Neurobiology and Behavior, Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA 92697-4545, USA.
2
Department of Molecular and Cell Biology, University of California, Merced, Merced, CA 95343, USA.
3
Plexxikon Inc., Berkeley, CA 94710, USA.
4
Department of Neurobiology and Behavior, Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA 92697-4545, USA. Electronic address: kngreen@uci.edu.

Abstract

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 ∼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.

PMID:
24742461
PMCID:
PMC4161285
DOI:
10.1016/j.neuron.2014.02.040
[Indexed for MEDLINE]
Free PMC Article
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