title: Oligomeric Aβ-induced microglial activation is possibly mediated by NADPH oxidase.
abstract: Recent studies have shown that oligomeric amyloid-β (oAβ) peptide can potentially activate microglia in addition to inducing more potent neurotoxicity compared with fibrillar Aβ (fAβ); however, its mechanisms of action remain unclear. This study was designed to investigate the possible mechanisms involved in the microglial activation induced by oAβ in BV-2 microglial cells. The results showed that oAβ induced activated properties of microglia, including higher proliferative capacity as well as increased production of reactive oxygen species, nitric oxide (NO), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β). NADPH oxidase inhibitors [diphenylene iodonium (DPI) and apocynin (4-hydroxy-3-methoxy-acetophenone)] prevented the microglial activation induced by oAβ, suggesting that NADPH oxidase activation was involved in microglial activation. In addition, TNF-α and IL-1β, 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 oAβ. In conclusion, microglial activation induced by oAβ is possibly mediated by NADPH oxidase, suggesting that oAβ, 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 oAβ-induced inflammatory neurodegeneration.
authors.affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, 103 Wenhua Road, Box 31, Shenyang 110016, People's Republic of China.
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.forename: Jing Yu
authors.initials: JY
authors.lastname: Yang
authors.forename: Xue Chun
authors.initials: XC
authors.lastname: Yao
authors.forename: Xue
authors.initials: X
authors.lastname: Xue
authors.forename: Qing Chun
authors.initials: QC
authors.lastname: Zhang
authors.forename: Xiao Xiao
authors.initials: XX
authors.lastname: Wang
authors.forename: Ling Ling
authors.initials: LL
authors.lastname: Ding
authors.forename: Chun Fu
authors.initials: CF
authors.lastname: Wu
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D051379:Mice; D017628:Microglia / Q000201:enzymology*; D019255:NADPH Oxidases / Q000502:physiology*; D019636:Neurodegenerative Diseases / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control; D010446:Peptide Fragments / Q000633:toxicity*; D055503:Protein Multimerization / Q000502:physiology
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D019255:NADPH Oxidases