Affiliated with Université Laval & CERVO Research Centre

Dynamics of spinal microglia repopulation following an acute depletion.

TitleDynamics of spinal microglia repopulation following an acute depletion.
Publication TypeJournal Article
Year of Publication2016
AuthorsYao Y, Echeverry S, Shi XQun, Yang M, Yang QZi, Wang GYun France, Chambon J, Wu YChen, Fu KYuan, De Koninck Y, Zhang J
JournalSci Rep
Date Published2016 Mar 10
KeywordsAnimals, Cytotoxicity, Immunologic, Immunotoxins, Inflammation, Male, Mice, Inbred C57BL, Microglia, Neuralgia, Peripheral Nerve Injuries, Ribosome Inactivating Proteins, Type 1, Sciatic Nerve, Spinal Cord

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.

Alternate JournalSci Rep
PubMed ID26961247
PubMed Central IDPMC4785356
Grant ListMOP-111129 / / Canadian Institutes of Health Research / Canada
MOP-12942 / / Canadian Institutes of Health Research / Canada