Nanoparticulate matter exposure results in white matter damage and an inflammatory microglial response in an experimental murine model.
Exposure to ambient air pollution has been associated with white matter damage and neurocognitive decline. However, the mechanisms of this injury are not well understood and remain largely uncharacterized in experimental models. Prior studies have shown that exposure to particulate matter (PM), a su...
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2021
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oai:doaj.org-article:dd6184e738a546fcb0c1be14f9bc13fe2021-12-02T20:15:41ZNanoparticulate matter exposure results in white matter damage and an inflammatory microglial response in an experimental murine model.1932-620310.1371/journal.pone.0253766https://doaj.org/article/dd6184e738a546fcb0c1be14f9bc13fe2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0253766https://doaj.org/toc/1932-6203Exposure to ambient air pollution has been associated with white matter damage and neurocognitive decline. However, the mechanisms of this injury are not well understood and remain largely uncharacterized in experimental models. Prior studies have shown that exposure to particulate matter (PM), a sub-fraction of air pollution, results in neuroinflammation, specifically the upregulation of inflammatory microglia. This study examines white matter and axonal injury, and characterizes microglial reactivity in the corpus callosum of mice exposed to 10 weeks (150 hours) of PM. Nanoscale particulate matter (nPM, aerodynamic diameter ≤200 nm) consisting primarily of traffic-related emissions was collected from an urban area in Los Angeles. Male C57BL/6J mice were exposed to either re-aerosolized nPM or filtered air for 5 hours/day, 3 days/week, for 10 weeks (150 hours; n = 18/group). Microglia were characterized by immunohistochemical double staining of ionized calcium-binding protein-1 (Iba-1) with inducible nitric oxide synthase (iNOS) to identify pro-inflammatory cells, and Iba-1 with arginase-1 (Arg) to identify anti-inflammatory/ homeostatic cells. Myelin injury was assessed by degraded myelin basic protein (dMBP). Oligodendrocyte cell counts were evaluated by oligodendrocyte transcription factor 2 (Olig2). Axonal injury was assessed by axonal neurofilament marker SMI-312. iNOS-expressing microglia were significantly increased in the corpus callosum of mice exposed to nPM when compared to those exposed to filtered air (2.2 fold increase; p<0.05). This was accompanied by an increase in dMBP (1.4 fold increase; p<0.05) immunofluorescent density, a decrease in oligodendrocyte cell counts (1.16 fold decrease; p<0.05), and a decrease in neurofilament SMI-312 (1.13 fold decrease; p<0.05) immunofluorescent density. Exposure to nPM results in increased inflammatory microglia, white matter injury, and axonal degradation in the corpus callosum of adult male mice. iNOS-expressing microglia release cytokines and reactive oxygen/ nitrogen species which may further contribute to the white matter damage observed in this model.Michelle ConnorKrista Lamorie-FooteQinghai LiuKristina ShkirkovaHans BaertschConstantinos SioutasTodd E MorganCaleb E FinchWilliam J MackPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 7, p e0253766 (2021) |
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Medicine R Science Q Michelle Connor Krista Lamorie-Foote Qinghai Liu Kristina Shkirkova Hans Baertsch Constantinos Sioutas Todd E Morgan Caleb E Finch William J Mack Nanoparticulate matter exposure results in white matter damage and an inflammatory microglial response in an experimental murine model. |
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Exposure to ambient air pollution has been associated with white matter damage and neurocognitive decline. However, the mechanisms of this injury are not well understood and remain largely uncharacterized in experimental models. Prior studies have shown that exposure to particulate matter (PM), a sub-fraction of air pollution, results in neuroinflammation, specifically the upregulation of inflammatory microglia. This study examines white matter and axonal injury, and characterizes microglial reactivity in the corpus callosum of mice exposed to 10 weeks (150 hours) of PM. Nanoscale particulate matter (nPM, aerodynamic diameter ≤200 nm) consisting primarily of traffic-related emissions was collected from an urban area in Los Angeles. Male C57BL/6J mice were exposed to either re-aerosolized nPM or filtered air for 5 hours/day, 3 days/week, for 10 weeks (150 hours; n = 18/group). Microglia were characterized by immunohistochemical double staining of ionized calcium-binding protein-1 (Iba-1) with inducible nitric oxide synthase (iNOS) to identify pro-inflammatory cells, and Iba-1 with arginase-1 (Arg) to identify anti-inflammatory/ homeostatic cells. Myelin injury was assessed by degraded myelin basic protein (dMBP). Oligodendrocyte cell counts were evaluated by oligodendrocyte transcription factor 2 (Olig2). Axonal injury was assessed by axonal neurofilament marker SMI-312. iNOS-expressing microglia were significantly increased in the corpus callosum of mice exposed to nPM when compared to those exposed to filtered air (2.2 fold increase; p<0.05). This was accompanied by an increase in dMBP (1.4 fold increase; p<0.05) immunofluorescent density, a decrease in oligodendrocyte cell counts (1.16 fold decrease; p<0.05), and a decrease in neurofilament SMI-312 (1.13 fold decrease; p<0.05) immunofluorescent density. Exposure to nPM results in increased inflammatory microglia, white matter injury, and axonal degradation in the corpus callosum of adult male mice. iNOS-expressing microglia release cytokines and reactive oxygen/ nitrogen species which may further contribute to the white matter damage observed in this model. |
format |
article |
author |
Michelle Connor Krista Lamorie-Foote Qinghai Liu Kristina Shkirkova Hans Baertsch Constantinos Sioutas Todd E Morgan Caleb E Finch William J Mack |
author_facet |
Michelle Connor Krista Lamorie-Foote Qinghai Liu Kristina Shkirkova Hans Baertsch Constantinos Sioutas Todd E Morgan Caleb E Finch William J Mack |
author_sort |
Michelle Connor |
title |
Nanoparticulate matter exposure results in white matter damage and an inflammatory microglial response in an experimental murine model. |
title_short |
Nanoparticulate matter exposure results in white matter damage and an inflammatory microglial response in an experimental murine model. |
title_full |
Nanoparticulate matter exposure results in white matter damage and an inflammatory microglial response in an experimental murine model. |
title_fullStr |
Nanoparticulate matter exposure results in white matter damage and an inflammatory microglial response in an experimental murine model. |
title_full_unstemmed |
Nanoparticulate matter exposure results in white matter damage and an inflammatory microglial response in an experimental murine model. |
title_sort |
nanoparticulate matter exposure results in white matter damage and an inflammatory microglial response in an experimental murine model. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2021 |
url |
https://doaj.org/article/dd6184e738a546fcb0c1be14f9bc13fe |
work_keys_str_mv |
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