Differences in the amyloid-beta-induced inflammatory response in microglia from C57BL/6 and A/J strains of mice.
The microglial inflammatory response to Abeta(1-42) stimulation with or without IFN-gamma priming was investigated in low and high responder strains of mice, A/J and C57BL/6, respectively. A/J microglia showed moderate morphological changes upon stimulation with IFN-gamma alone or with Abeta(1-42). Conversely, C57BL/6 microglia showed major changes in their cellular morphology, which were accompanied by a decrease in NO release and a marked increase in TNF-alpha production. These results indicate that the magnitude of the microglial inflammatory response to Abeta is strongly influenced by genetic factors. Individual differences in the regulation of the microglial response may be a key player in the rate of development of the neuropathology of AD.
Dudal
Sherri
S
Department of Experimental Medicine, McGill University, Montréal, Québec, Canada H3A 2T5.
Morissette
Céline
C
Lacombe
Diane
D
Tremblay
Patrick
P
Gervais
Francine
F
D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000633:toxicity*; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D004357:Drug Synergism; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D007150:Immunohistochemistry / Q000379:methods; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D007371:Interferon-gamma / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL / Q000276:immunology*; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016253:Microscopy, Immunoelectron / Q000379:methods; D009573:Nitrites / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism / Q000633:toxicity*; D013045:Species Specificity; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016229:Amyloid beta-Peptides; D009573:Nitrites; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; C075222:amyloid beta-protein (1-42); D007371:Interferon-gamma