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Rotenone directly induces BV2 cell activation via the p38 MAPK pathway
Feng Gao1, Dong Chen, Qingsong Hu
1Laboratory of Molecular Neuropathology, Key Laboratory of Brain Function and Diseases and School of Life Sciences, University of Science & Technology of China, Chinese Academy of Sciences, Hefei, China.
Plos One
|August 27, 2013
Summary
Environmental toxins like rotenone directly activate microglia, a key inflammatory cell in Parkinson's disease (PD). This activation involves the NF-κB and p38 MAPK pathways, driven by reactive oxygen species (ROS).
Area of Science:
- Neuroscience
- Toxicology
- Immunology
Background:
- Parkinson's disease (PD) pathogenesis involves neuroinflammation and microglial activation.
- Mitochondrial dysfunction, potentially induced by environmental toxins, is implicated in PD.
- The precise mechanisms by which toxins activate microglia remain incompletely understood.
Purpose of the Study:
- To investigate the direct effects of rotenone, a mitochondrial complex I inhibitor, on microglial activation.
- To elucidate the signaling pathways involved in rotenone-induced microglial activation.
Main Methods:
- Utilized rotenone as a model environmental toxin.
- Investigated the role of nuclear factor kappa B (NF-κB) and p38 mitogen-activated protein kinase (MAPK) signaling pathways.
- Assessed the involvement of reactive oxygen species (ROS) in the activation process.
Main Results:
- Rotenone directly activates microglia via the NF-κB pathway, increasing inflammatory cytokine expression.
- Rotenone induces caspase-1 activation and IL-1β release, dependent on p38 MAPK.
- p38 MAPK activation is linked to rotenone-induced ROS production; ROS scavenging inhibits microglial activation.
Conclusions:
- Environmental toxins like rotenone can directly trigger microglial activation.
- The p38 MAPK pathway, modulated by ROS, is a critical mediator of rotenone-induced neuroinflammation.
- These findings offer insights into the environmental triggers of neuroinflammation in Parkinson's disease.
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