Diverse microglial responses after intrahippocampal administration of lipopolysaccharide.
Inflammation has been argued to play a primary role in the pathogenesis of Alzheimer's disease by contributing to the development of neuropathology and clinical symptoms. However, the mechanisms underlying these effects remain obscure. Lipopolysaccharide (LPS) activates the innate immune response and triggers gliosis when injected into the central nervous system. In the studies described in the present work, we evaluated the time course of microgliosis after a single intrahippocampal injection of LPS. Mice were injected bilaterally with 4 mug of LPS. Post-injection survival times were 1, 6, and 24 h, as well as 3, 7, 14, and 28 days. Protein and RNA analyses were performed for inflammatory markers. Significant elevations of cluster differentiation marker CD45, glial fibrillary acidic protein (GFAP), scavenger receptor A (SRA), and Fcgamma receptor mRNA were seen after 24 h. Immunohistochemistry revealed a complex pattern of protein expression by microglia, as well as changes in cell morphologies. RNA and protein for Fcgamma receptor and SRA were transiently elevated, peaked at 3 days, and returned to basal levels after 1 week. In contrast, microglia remained significantly activated through the 28-day time point, as determined by CD45 and complement receptor 3 levels. These findings indicate a multivariate response to LPS, and evaluation of microglial phenotypes may lead to a better understanding of neuroinflammatory diseases.
Herber
Donna L
DL
Department of Pharmacology and Therapeutics, Alzheimer Research Laboratory, University of South Florida, Tampa, USA.
Maloney
Jessica L
JL
Roth
Lisa M
LM
Freeman
Melissa J
MJ
Morgan
Dave
D
Gordon
Marcia N
MN
D000818:Animals; D015415:Biomarkers; D016207:Cytokines / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects*; D007150:Immunohistochemistry; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology*; D008262:Macrophage Activation / Q000187:drug effects; D016177:Macrophage-1 Antigen / Q000378:metabolism; D051379:Mice; D017628:Microglia / Q000187:drug effects*; D008845:Microinjections; D012313:RNA / Q000032:analysis / Q000096:biosynthesis; D017452:Receptors, IgG / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051117:Scavenger Receptors, Class A / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013534:Survival; D051197:Toll-Like Receptor 4 / Q000378:metabolism
D015415:Biomarkers; D016207:Cytokines; D005904:Glial Fibrillary Acidic Protein; D008070:Lipopolysaccharides; D016177:Macrophage-1 Antigen; C034477:RNA primers; D017452:Receptors, IgG; D051117:Scavenger Receptors, Class A; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D012313:RNA; D017493:Leukocyte Common Antigens