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Macrophages treated with particulate matter PM2.5 induce selective neurotoxicity through glutaminase-mediated glutamate generation.
- Source :
- Journal of Neurochemistry; Jul2015, Vol. 134 Issue 2, p315-326, 12p
- Publication Year :
- 2015
-
Abstract
- Exposure to atmospheric particulate matter PM<subscript>2.5</subscript> (aerodynamic diameter < 2.5 lm) has been epidemiologically associated with respiratory illnesses. However, recent data have suggested that PM<subscript>2.5</subscript> 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 PM<subscript>2.5</subscript> causes neurotoxicity remains unclear. In this study, we have demonstrated that PM<subscript>2.5</subscript> impairs the tight junction of endothelial cells and increases permeability and monocyte transmigration across endothelial monolayer in vitro, indicating thatPM<subscript>2.5</subscript> is able to disrupt blood-brain barrier integrity and gain access to the CNS. Exposure of primary neuronal cultures to PM<subscript>2.5</subscript> resulted in decrease in cell viability and loss of neuronal antigens. Furthermore, supernatants collected from PM<subscript>2.5</subscript>-treated macrophages and microglia were also neurotoxic. These macrophages and microglia significantly increased extracellular levels of glutamate following PM<subscript>2.5</subscript> exposure, which were negatively correlated with neuronal viability. Pre-treatment with NMDA receptor antagonist MK801 alleviated neuron loss, suggesting that PM<subscript>2.5</subscript> 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 PM<subscript>2.5</subscript>-treated macrophages and increased in extracellular vesicles, suggesting that PM<subscript>2.5</subscript> induces glutaminase release through extracellular vesicles. In conclusion, these findings indicatePM<subscript>2.5</subscript> as a potential neurotoxic factor, crucial to understanding the effects of air pollution on the CNS. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00223042
- Volume :
- 134
- Issue :
- 2
- Database :
- Complementary Index
- Journal :
- Journal of Neurochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 108763649
- Full Text :
- https://doi.org/10.1111/jnc.13135