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Updated: May 16, 2026
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Oligomeric Aβ-induced microglial activation is possibly mediated by NADPH oxidase
Juan Li1, Jing Yu Yang, Xue Chun Yao
1Department of Pharmacology, Shenyang Pharmaceutical University, 103 Wenhua Road, Box 31, Shenyang 110016, People's Republic of China.
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.
Insights
Oligomeric amyloid-β (oAβ) activates microglia via NADPH oxidase, leading to inflammation and potential neurodegeneration in Alzheimer's disease. Targeting NADPH oxidase may prevent this damage.
Area of Science:
- Neuroscience
- Immunology
- Biochemistry
Background:
- Oligomeric amyloid-β (oAβ) shows greater neurotoxicity than fibrillar Aβ (fAβ).
- Mechanisms of microglial activation by oAβ are not fully understood.
- Microglia play a crucial role in neuroinflammation and neurodegenerative diseases.
Purpose of the Study:
- To investigate the mechanisms of microglial activation induced by oAβ.
- To explore the role of NADPH oxidase in oAβ-mediated microglial activation.
- To understand the self-regulatory cycle of microglial activation.
Main Methods:
- Utilized BV-2 microglial cell line.
- Administered oAβ and measured microglial activation markers (proliferation, ROS, NO, TNF-α, IL-1β).
- Employed NADPH oxidase inhibitors (DPI, apocynin) to assess their effects.
Main Results:
- oAβ induced microglial activation, increasing proliferation, ROS, NO, TNF-α, and IL-1β production.
- NADPH oxidase inhibitors blocked oAβ-induced microglial activation.
- Released TNF-α and IL-1β further activated microglia, creating a self-cycle regulated by NADPH oxidase.
Conclusions:
- Microglial activation by oAβ is mediated by NADPH oxidase.
- oAβ contributes to indirect neuronal damage via pro-inflammatory microglial activation.
- NADPH oxidase is a potential therapeutic target for preventing oAβ-induced neurodegeneration in Alzheimer's disease.
