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...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Michelle Connor, Krista Lamorie-Foote, Qinghai Liu, Kristina Shkirkova, Hans Baertsch, Constantinos Sioutas, Todd E Morgan, Caleb E Finch, William J Mack
Formato: article
Lenguaje:EN
Publicado: Public Library of Science (PLoS) 2021
Materias:
R
Q
Acceso en línea:https://doaj.org/article/dd6184e738a546fcb0c1be14f9bc13fe
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:dd6184e738a546fcb0c1be14f9bc13fe
record_format dspace
spelling 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)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle 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.
description 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 AT michelleconnor nanoparticulatematterexposureresultsinwhitematterdamageandaninflammatorymicroglialresponseinanexperimentalmurinemodel
AT kristalamoriefoote nanoparticulatematterexposureresultsinwhitematterdamageandaninflammatorymicroglialresponseinanexperimentalmurinemodel
AT qinghailiu nanoparticulatematterexposureresultsinwhitematterdamageandaninflammatorymicroglialresponseinanexperimentalmurinemodel
AT kristinashkirkova nanoparticulatematterexposureresultsinwhitematterdamageandaninflammatorymicroglialresponseinanexperimentalmurinemodel
AT hansbaertsch nanoparticulatematterexposureresultsinwhitematterdamageandaninflammatorymicroglialresponseinanexperimentalmurinemodel
AT constantinossioutas nanoparticulatematterexposureresultsinwhitematterdamageandaninflammatorymicroglialresponseinanexperimentalmurinemodel
AT toddemorgan nanoparticulatematterexposureresultsinwhitematterdamageandaninflammatorymicroglialresponseinanexperimentalmurinemodel
AT calebefinch nanoparticulatematterexposureresultsinwhitematterdamageandaninflammatorymicroglialresponseinanexperimentalmurinemodel
AT williamjmack nanoparticulatematterexposureresultsinwhitematterdamageandaninflammatorymicroglialresponseinanexperimentalmurinemodel
_version_ 1718374554984775680