AbstractBackground: As part of their innate immune response to changes in the central nervous system environment, normally quiescent microglia become activated and increase expression of pattern recognition receptors, scavenger receptors, and production of inflammatory cytokines, proteinases, reactive oxygen species (ROS), and free radicals. These molecules have been implicated in the pathogenesis and progression of several neurodegenerative disorders including Alzheimer disease (AD).Objective: We compared patterns of microglial innate immune responses elicited by nonfibrillar amyloid β peptide (nfAβ1-42) to those elicited by lipopolysaccharide (LPS).Methods: Murine BV-2 microglial cells were exposed to either nfAβ1-42or LPS for 12 h. Then, total RNA from each condition was isolated and expression levels of Toll-like receptor (TLR)-4, scavenger receptor class A (SRMARCO) and class B (SR-BI), CD36, and matrix metalloproteinase (MMP)-9 were determined by reverse transcription-quantitative real-time polymerase chain reaction. The amount of hydrogen peroxide (H2O2) and nitric oxide (NO) in the cell-free supernatant at 24 h were determined using 10-acetyl-3,7-dihydroxyphenoxazine (Amplex Red) and Griess reagent, respectively.Results: nfAβ1-42and LPS significantly increased expression of TLR-4, SR-MARCO, CD36, and MMP-9 and production of H2O2 and NO in BV-2 microglial cells compared with that of unstimulated cells. However, expression of SR-BI was significantly induced only when the cells were exposed to nfAβ1-42.Conclusion: These findings indicate that pattern of microglial innate immune responses elicited by nfAβ1-42overlap with that elicited by LPS and suggest a specific role of microglial SR-BI expression in AD pathogenesis.
Ultrasonic force microscopy for nanomechanical characterization of early and late-stage amyloid-β peptide aggregation
