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Sci Rep. 2016 Mar 10;6:22839. doi: 10.1038/srep22839.

Dynamics of spinal microglia repopulation following an acute depletion.

Author information

1
The Alan Edwards Centre for Research on Pain, McGill University, Montreal, QC, Canada.
2
Center for TMD &Orofacial Pain, Peking University School &Hospital of Stomatology, Beijing, China.
3
Faculty of Dentistry, McGill University, Montreal, QC, Canada.
4
Institut universitaire en santé mentale de Québec, QC G1J 2G3, Canada.
5
Department of Psychiatry &Neuroscience, Université Laval, Québec, G1V 0A6, Canada.
6
Department of Neurology &Neurosurgery, McGill University, Montreal, QC, Canada.

Abstract

Our understanding on the function of microglia has been revolutionized in the recent 20 years. However, the process of maintaining microglia homeostasis has not been fully understood. In this study, we dissected the features of spinal microglia repopulation following an acute partial depletion. By injecting intrathecally Mac-1-saporin, a microglia selective immunotoxin, we ablated 50% microglia in the spinal cord of naive mice. Spinal microglia repopulated rapidly and local homeostasis was re-established within 14 days post-depletion. Mac-1-saporin treatment resulted in microglia cell proliferation and circulating monocyte infiltration. The latter is indeed part of an acute, transient inflammatory reaction that follows cell depletion, and was characterized by an increase in the expression of inflammatory molecules and by the breakdown of the blood spinal cord barrier. During this period, microglia formed cell clusters and exhibited a M1-like phenotype. MCP-1/CCR2 signaling was essential in promoting this depletion associated spinal inflammatory reaction. Interestingly, ruling out MCP-1-mediated secondary inflammation, including blocking recruitment of monocyte-derived microglia, did not affect depletion-triggered microglia repopulation. Our results also demonstrated that newly generated microglia kept their responsiveness to peripheral nerve injury and their contribution to injury-associated neuropathic pain was not significantly altered.

PMID:
26961247
PMCID:
PMC4785356
DOI:
10.1038/srep22839
[Indexed for MEDLINE]
Free PMC Article

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