Axonal lesion-induced microglial proliferation and microglial cluster formation in the mouse.
Microglia are innate immune cells and form the first line of defense of the CNS. Proliferation is a key event in the activation of microglia in acute pathology, and has been extensively characterized in rats, but not in mice. In this study we investigated axonal-lesion-induced microglial proliferation and surface antigen expression in C57BL/6 mice. Transection of the entorhino-dentate perforant path projection results in an anterograde axonal and a dense terminal degeneration that induces a region-specific activation of microglia in the dentate gyrus. Time-course analysis showed activation of microglial cells within the first week post-lesion and cell counting demonstrated a significant 1.6-fold increase in microglial numbers 24 h post-lesion reaching a maximal 3.8-fold increase 3 days post-lesion compared with controls. Double staining for the microglial macrophage antigen-1 and the proliferation marker bromodeoxyuridine, injected 1 h prior to perfusion, showed that lesion-reactive microglia accounted for the vast majority of proliferating cells. Microglia proliferated as soon as 24 h after lesion and 25% of all microglial cells were proliferating 3 days post-lesion. Immunofluorescence double staining showed that most activated, proliferating microglia occurred in multicellular clusters and co-expressed the intercellular adhesion molecule-1 and the hematopoietic stem cell marker cluster of differentiation 34. In conclusion, this study extends observations of axonal lesion-induced microglial proliferation in rats to mice, and provides new information on early microglial proliferation and microglial cluster formation and surface antigen expression in the mouse.
Dissing-Olesen
L
L
Medical Biotechnology Center, University of Southern Denmark, Winsloewparken 25, 2, DK-5000 Odense, Denmark. ldolesen@health.sdu.dk
Ladeby
R
R
Nielsen
H H
HH
Toft-Hansen
H
H
Dalmau
I
I
Finsen
B
B
D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D001369:Axons / Q000473:pathology*; D001973:Bromodeoxyuridine / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D049109:Cell Proliferation; D005452:Fluoresceins; D005786:Gene Expression Regulation / Q000502:physiology*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000502:physiology*; D009930:Organic Chemicals; D019580:Perforant Pathway / Q000293:injuries* / Q000473:pathology; D013997:Time Factors
D018952:Antigens, CD34; D002135:Calcium-Binding Proteins; D005452:Fluoresceins; D016177:Macrophage-1 Antigen; D009930:Organic Chemicals; C435731:fluoro jade; D018799:Intercellular Adhesion Molecule-1; D001973:Bromodeoxyuridine