Oligomeric Aβ-Induced Microglial Activation is Possibly Mediated by NADPH Oxidase

Recent studies have shown that oligomeric amyloid-beta (oA beta) peptide can potentially activate microglia in addition to inducing more potent neurotoxicity compared with fibrillar A beta (fA beta); however, its mechanisms of action remain unclear. This study was designed to investigate the possible mechanisms involved in the microglial activation induced by oA beta in BV-2 microglial cells. The results showed that oA beta induced activated properties of microglia, including higher proliferative capacity as well as increased production of reactive oxygen species, nitric oxide (NO), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1 beta (IL-1 beta). NADPH oxidase inhibitors [diphenylene iodonium (DPI) and apocynin (4-hydroxy-3-methoxy-acetophenone)] prevented the microglial activation induced by oA beta, suggesting that NADPH oxidase activation was involved in microglial activation. In addition, TNF-alpha and IL-1 beta, which are massively released by activated microglia, significantly induced the activation of microglia, thereby resulting in the production of NO and proliferation of microglia, respectively. These effects could be inhibited by diphenylene iodonium and apocynin, indicating a self-cycle regulated by NADPH oxidase in microglial activation in response to oA beta. In conclusion, microglial activation induced by oA beta is possibly mediated by NADPH oxidase, suggesting that oA beta, which is normally considered a neurotoxin, may also lead to indirect neuronal damage through the pro-inflammation activation of microglia in Alzheimer's disease and that NADPH oxidase could be a potential target to prevent oA beta-induced inflammatory neurodegeneration.