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Updated: Apr 6, 2026
Microglia as a Surrogate Biosensor to Determine Nanoparticle Neurotoxicity
Published on: October 25, 2016
Trimethyltin-Induced Microglial Activation via NADPH Oxidase and MAPKs Pathway in BV-2 Microglial Cells
1Department of Pharmacology, Seoul National University College of Medicine, 103 Daehakno, Jongno-gu, Seoul 110-799, Republic of Korea.
Abstract:
Trimethyltin (TMT) is known as a potent neurotoxicant that causes neuronal cell death and neuroinflammation, particularly in the hippocampus. Microglial activation is one of the prominent pathological features of TMT neurotoxicity. Nevertheless, it remains unclear how microglial activation occurs in TMT intoxication. In this study, we aimed to investigate the signaling pathways in TMT-induced microglial activation using BV-2 murine microglial cells. Our results revealed that TMT generates reactive oxygen species (ROS) and increases the expression of CD11b and nuclear factor-κB- (NF-κB-) mediated nitric oxide (NO) and tumor necrosis factor- (TNF-) α in BV-2 cells. We also observed that NF-κB activation was controlled by p38 and JNK phosphorylation. Moreover, TMT-induced ROS generation occurred via nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in BV-2 cells. Interestingly, treatment with the NADPH oxidase inhibitor apocynin significantly suppressed p38 and JNK phosphorylation and NF-κB activation and ultimately the production of proinflammatory mediators upon TMT exposure. These findings indicate that NADPH oxidase-dependent ROS generation activated p38 and JNK mitogen-activated protein kinases (MAPKs), which then stimulated NF-κB to release proinflammatory mediators in the TMT-treated BV-2 cells.
Insights
Trimethyltin (TMT) causes neuroinflammation by activating microglia. This study reveals TMT-induced reactive oxygen species (ROS) activate specific signaling pathways, leading to the release of inflammatory mediators.
Area of Science:
- Neuroscience
- Toxicology
- Cell Biology
Background:
- Trimethyltin (TMT) is a neurotoxicant causing neuronal damage and neuroinflammation, particularly in the hippocampus.
- Microglial activation is a key pathological feature of TMT neurotoxicity, but the underlying mechanisms remain unclear.
Purpose of the Study:
- To investigate the signaling pathways involved in TMT-induced microglial activation.
- To elucidate the role of reactive oxygen species (ROS) and specific kinases in this process using BV-2 murine microglial cells.
Main Methods:
- BV-2 murine microglial cells were exposed to TMT.
- Analysis of ROS generation, CD11b expression, and NF-κB activation.
- Investigation of p38 and JNK phosphorylation and the effect of NADPH oxidase inhibition (apocynin).
Main Results:
- TMT exposure induced ROS generation via NADPH oxidase in BV-2 cells.
- TMT increased CD11b expression and NF-κB-mediated production of nitric oxide (NO) and tumor necrosis factor-α (TNF-α).
- ROS generation activated p38 and JNK mitogen-activated protein kinases (MAPKs), leading to NF-κB activation and subsequent release of inflammatory mediators. Apocynin treatment suppressed these effects.
Conclusions:
- NADPH oxidase-dependent ROS generation is a critical upstream event in TMT-induced microglial activation.
- The pathway involves ROS activating p38/JNK MAPKs, which in turn activate NF-κB, leading to the release of pro-inflammatory mediators.
- Targeting NADPH oxidase may offer a therapeutic strategy against TMT neurotoxicity.
