Reactive microgliosis engages distinct responses by microglial subpopulations after minor central nervous system injury.
Microglia are bone marrow-derived cells that constitute a facultative macrophage population when activated by trauma or pathology in the CNS. Endogenous CNS-resident microglia as well as exogenous (immigrant) bone marrow-derived cells contribute to reactive microgliosis, raising fundamental questions about the cellular composition, kinetics, and functional characteristics of the reactive microglial cell population. Bone marrow chimeric mice reconstituted with green fluorescent protein-expressing (GFP(+)) donor bone marrow cells were subjected to entorhinal cortex lesion, resulting in selective axonal degeneration and a localized microglial reaction in the hippocampus. Flow cytometric evaluation of individually dissected hippocampi differentiated immigrant GFP(+) microglia from resident GFP(-) microglia (CD11b(+)CD45(dim)) and identified a subset of mainly resident CD11b(+) microglia that was induced to express CD34. The proportion of immigrant GFP(+) microglia (CD11b(+)CD45(dim)) increased signficantly by 3 and 5 days postlesion and reached a maximum of 13% by 7 days. These cells expressed lower CD11b levels than resident microglia, forming a distinct subpopulation on CD11b/CD45 profiles. The proportion of CD34(+)CD11b(+) microglia was significantly increased at 3 days postlesion but had normalized by 5 and 7 days, when the microglial reaction is known to be at its maximum. Our results show that distinct subpopulations of microglia respond to minor CNS injury. The heterogeneity in microglial response may have functional consequences for repair and possibly therapy.
Wirenfeldt
Martin
M
Medical Biotechnology Center, University of Southern Denmark, Odense. mwnielsen@health.sdu.dk
Babcock
Alicia Anne
AA
Ladeby
Rune
R
Lambertsen
Kate Lykke
KL
Dagnaes-Hansen
Frederik
F
Leslie
Robert Graham Quinton
RG
Owens
Trevor
T
Finsen
Bente
B
D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D016026:Bone Marrow Transplantation / Q000379:methods; D039481:CD11b Antigen / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology; D002493:Central Nervous System Diseases / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D005434:Flow Cytometry / Q000379:methods; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000502:physiology*; D013997:Time Factors
D018952:Antigens, CD34; D039481:CD11b Antigen; D049452:Green Fluorescent Proteins