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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2016

Open Access 01-12-2016 | Research

Urban traffic-derived nanoparticulate matter reduces neurite outgrowth via TNFα in vitro

Authors: Hank Cheng, David A. Davis, Sina Hasheminassab, Constantinos Sioutas, Todd E. Morgan, Caleb E. Finch

Published in: Journal of Neuroinflammation | Issue 1/2016

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Abstract

Background

The basis for air pollution-associated neurodegenerative changes in humans is being studied in rodent models. We and others find that the ultrafine particulate matter (PM) derived from vehicular exhaust can induce synaptic dysfunction and inflammatory responses in vivo and in vitro. In particular, a nano-sized subfraction of particulate matter (nPM, PM0.2) from a local urban traffic corridor can induce glial TNFα production in mixed glia (astrocytes and microglia) derived from neonatal rat cerebral cortex.

Methods

Here, we examine the role of TNFα in neurite dysfunctions induced by nPM in aqueous suspensions at 12 μg/ml. First, we show that the proximal brain gateway to nPM, the olfactory neuroepithelium (OE), rapidly responds to nPM ex vivo, with induction of TNFα, activation of macrophages, and dendritic shrinkage. Cell interactions were further analyzed with mixed glia and neurons from neonatal rat cerebral cortex.

Results

Microglia contributed more than astrocytes to TNFα induction by nPM. We then showed that the threefold higher TNFα in conditioned media (nPM-CM) from mixed glia was responsible for the inhibition of neurite outgrowth by small interfering RNA (siRNA) TNFα knockdown and by TNFα immunoneutralization. Despite lack of TNFR1 induction by nPM in the OE, experimental blocking of TNFR1 by TNFα receptor blockers restored total neurite length.

Conclusions

These findings implicate microglia-derived TNFα as a mediator of nPM in air pollution-associated neurodegenerative changes which alter synaptic functions and neuronal growth.
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Metadata
Title
Urban traffic-derived nanoparticulate matter reduces neurite outgrowth via TNFα in vitro
Authors
Hank Cheng
David A. Davis
Sina Hasheminassab
Constantinos Sioutas
Todd E. Morgan
Caleb E. Finch
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2016
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-016-0480-3

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