Prevention of C5aR1 signaling delays microglial inflammatory polarization, favors clearance pathways and suppresses cognitive loss ...
Abstract Background Pharmacologic inhibition of C5aR1, a receptor for the complement activation proinflammatory fragment, C5a, suppressed pathology and cognitive deficits in Alzheimer's disease (AD) mouse models. To validate that the effect of the antagonist was specifically via C5aR1 inhibitio...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article in Journal/Newspaper |
| Language: | unknown |
| Published: |
figshare
2017
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| Subjects: | |
| Online Access: | https://dx.doi.org/10.6084/m9.figshare.c.3882769.v1 https://springernature.figshare.com/collections/Prevention_of_C5aR1_signaling_delays_microglial_inflammatory_polarization_favors_clearance_pathways_and_suppresses_cognitive_loss/3882769/1 |
| Summary: | Abstract Background Pharmacologic inhibition of C5aR1, a receptor for the complement activation proinflammatory fragment, C5a, suppressed pathology and cognitive deficits in Alzheimer's disease (AD) mouse models. To validate that the effect of the antagonist was specifically via C5aR1 inhibition, mice lacking C5aR1 were generated and compared in behavior and pathology. In addition, since C5aR1 is primarily expressed on cells of the myeloid lineage, and only to a lesser extent on endothelial cells and neurons in brain, gene expression in microglia isolated from adult brain at multiple ages was compared across all genotypes. Methods C5aR1 knock out mice were crossed to the Arctic AD mouse model, and characterized for pathology and for behavior performance in a hippocampal dependent memory task. CX3CR1GFP and CCR2RFP reporter mice were bred to C5aR1 sufficient and knockout wild type and Arctic mice to enable sorting of microglia (GFP-positive, RFP-negative) isolated from adult brain at 2, 5, 7 and 10 months of ... |
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