title: Dynamics of spinal microglia repopulation following an acute depletion.
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.
authors.affiliation: The Alan Edwards Centre for Research on Pain, McGill University, Montreal, QC, Canada.|Center for TMD &Orofacial Pain, Peking University School &Hospital of Stomatology, Beijing, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Yao
authors.affiliation: The Alan Edwards Centre for Research on Pain, McGill University, Montreal, QC, Canada.
authors.forename: Stefania
authors.initials: S
authors.lastname: Echeverry
authors.affiliation: The Alan Edwards Centre for Research on Pain, McGill University, Montreal, QC, Canada.
authors.forename: Xiang Qun
authors.initials: XQ
authors.lastname: Shi
authors.affiliation: The Alan Edwards Centre for Research on Pain, McGill University, Montreal, QC, Canada.
authors.forename: Mu
authors.initials: M
authors.lastname: Yang
authors.affiliation: The Alan Edwards Centre for Research on Pain, McGill University, Montreal, QC, Canada.
authors.forename: Qiu Zi
authors.initials: QZ
authors.lastname: Yang
authors.affiliation: The Alan Edwards Centre for Research on Pain, McGill University, Montreal, QC, Canada.|Faculty of Dentistry, McGill University, Montreal, QC, Canada.
authors.forename: Guan Yun Frances
authors.initials: GY
authors.lastname: Wang
authors.affiliation: The Alan Edwards Centre for Research on Pain, McGill University, Montreal, QC, Canada.
authors.forename: Julien
authors.initials: J
authors.lastname: Chambon
authors.affiliation: The Alan Edwards Centre for Research on Pain, McGill University, Montreal, QC, Canada.
authors.forename: Yi Chen
authors.initials: YC
authors.lastname: Wu
authors.affiliation: Center for TMD &Orofacial Pain, Peking University School &Hospital of Stomatology, Beijing, China.
authors.forename: Kai Yuan
authors.initials: KY
authors.lastname: Fu
authors.affiliation: The Alan Edwards Centre for Research on Pain, McGill University, Montreal, QC, Canada.|Institut universitaire en santé mentale de Québec, QC G1J 2G3, Canada.|Department of Psychiatry &Neuroscience, Université Laval, Québec, G1V 0A6, Canada.
authors.forename: Yves
authors.initials: Y
authors.lastname: De Koninck
authors.affiliation: The Alan Edwards Centre for Research on Pain, McGill University, Montreal, QC, Canada.|Department of Neurology &Neurosurgery, McGill University, Montreal, QC, Canada.|Faculty of Dentistry, McGill University, Montreal, QC, Canada.
authors.forename: Ji
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D003602:Cytotoxicity, Immunologic; D000922:Immunotoxins / Q000633:toxicity; D007249:Inflammation / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000473:pathology*; D009437:Neuralgia / Q000473:pathology / Q000503:physiopathology; D059348:Peripheral Nerve Injuries / Q000473:pathology / Q000503:physiopathology; D054789:Ribosome Inactivating Proteins, Type 1 / Q000633:toxicity; D000076985:Saporins; D012584:Sciatic Nerve / Q000293:injuries; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology*
chemical_list: D000922:Immunotoxins; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins