Related Experiment Video
Updated: Apr 14, 2026
Microglia as a Surrogate Biosensor to Determine Nanoparticle Neurotoxicity
Published on: October 25, 2016
Macrophages treated with particulate matter PM2.5 induce selective neurotoxicity through glutaminase-mediated
Fang Liu1,2, Yunlong Huang3,4, Fang Zhang1,2
1Laboratory of Environment and Health, University of Chinese Academy of Sciences, Beijing, China.
Abstract:
Exposure to atmospheric particulate matter PM2.5 (aerodynamic diameter ≤ 2.5 μm) has been epidemiologically associated with respiratory illnesses. However, recent data have suggested that PM2.5 is able to infiltrate into circulation and elicit a systemic inflammatory response. Potential adverse effects of air pollutants to the central nervous system (CNS) have raised concerns, but whether PM2.5 causes neurotoxicity remains unclear. In this study, we have demonstrated that PM2.5 impairs the tight junction of endothelial cells and increases permeability and monocyte transmigration across endothelial monolayer in vitro, indicating that PM2.5 is able to disrupt blood-brain barrier integrity and gain access to the CNS. Exposure of primary neuronal cultures to PM2.5 resulted in decrease in cell viability and loss of neuronal antigens. Furthermore, supernatants collected from PM2.5 -treated macrophages and microglia were also neurotoxic. These macrophages and microglia significantly increased extracellular levels of glutamate following PM2.5 exposure, which were negatively correlated with neuronal viability. Pre-treatment with NMDA receptor antagonist MK801 alleviated neuron loss, suggesting that PM2.5 neurotoxicity is mediated by glutamate. To determine the potential source of excess glutamate production, we investigated glutaminase, the main enzyme for glutamate generation. Glutaminase was reduced in PM2.5 -treated macrophages and increased in extracellular vesicles, suggesting that PM2.5 induces glutaminase release through extracellular vesicles. In conclusion, these findings indicate PM2.5 as a potential neurotoxic factor, crucial to understanding the effects of air pollution on the CNS.
Insights
Fine particulate matter (PM2.5) can damage the blood-brain barrier and harm brain cells. This study reveals PM2.5-induced glutamate release from immune cells causes neurotoxicity, impacting central nervous system health.
Area of Science:
- Environmental Health
- Neuroscience
- Toxicology
Background:
- Particulate matter (PM2.5) exposure is linked to respiratory issues.
- Emerging evidence suggests PM2.5 may affect the central nervous system (CNS).
- The neurotoxic potential of PM2.5 remains incompletely understood.
Purpose of the Study:
- To investigate whether PM2.5 causes neurotoxicity.
- To elucidate the mechanisms underlying PM2.5-induced neurotoxicity.
- To assess PM2.5's impact on blood-brain barrier integrity.
Main Methods:
- In vitro assessment of PM2.5 effects on endothelial cells and neuronal cultures.
- Analysis of inflammatory mediators released by PM2.5-exposed macrophages and microglia.
- Investigation of glutamate levels and NMDA receptor involvement.
- Examination of glutaminase activity and extracellular vesicle release.
Main Results:
- PM2.5 disrupted endothelial cell tight junctions, increasing blood-brain barrier permeability.
- PM2.5 exposure reduced neuronal viability and antigen expression.
- Supernatants from PM2.5-treated immune cells were neurotoxic, correlating with increased extracellular glutamate.
- NMDA receptor antagonism mitigated PM2.5-induced neurotoxicity.
- PM2.5 exposure altered glutaminase levels and promoted its release via extracellular vesicles.
Conclusions:
- PM2.5 can compromise blood-brain barrier integrity, allowing CNS entry.
- PM2.5 induces neurotoxicity mediated by glutamate released from activated immune cells.
- Glutaminase dysregulation and extracellular vesicle-mediated release contribute to PM2.5 neurotoxicity.
- These findings highlight PM2.5 as a significant neurotoxic factor in air pollution impacting CNS health.
