Particulate Matter Exacerbates the Death of Dopaminergic Neurons in Parkinson’s Disease through an Inflammatory Response

Particulate matter (PM), a component of air pollution, has been epidemiologically associated with a variety of diseases. Recent reports reveal that PM has detrimental effects on the brain. In this study, we aimed to investigate the biological effects of ambient particles on the neurodegenerative dis...

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Main Authors: Dabin Choi, Gaheon Lee, Kyung Hwa Kim, Hyunsu Bae
Format: Article
Language:English
Published: MDPI AG 2022-06-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/23/12/6487
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author Dabin Choi
Gaheon Lee
Kyung Hwa Kim
Hyunsu Bae
author_facet Dabin Choi
Gaheon Lee
Kyung Hwa Kim
Hyunsu Bae
author_sort Dabin Choi
collection DOAJ
description Particulate matter (PM), a component of air pollution, has been epidemiologically associated with a variety of diseases. Recent reports reveal that PM has detrimental effects on the brain. In this study, we aimed to investigate the biological effects of ambient particles on the neurodegenerative disease Parkinson’s disease (PD). We exposed mice to coarse particles (PM<sub>10</sub>: 2.5–10 μm) for short (5 days) and long (8 weeks) durations via intratracheal instillation. Long-term PM<sub>10</sub> exposure exacerbated motor impairment and dopaminergic neuron death in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse models. Short-term PM<sub>10</sub> exposure resulted in both pulmonary and systemic inflammatory responses in mice. We further investigated the mechanism underlying PM<sub>10</sub>-induced neurotoxicity in cocultures of lung LA-4 epithelial cells and RAW264.7 macrophages. PM<sub>10</sub> treatment elicited a dramatic increase in proinflammatory mediators in LA-4/RAW264.7 coculture. Treating BV2 microglial cells with PM<sub>10</sub>-treated conditioned medium induced microglial activation. Furthermore, 1-methyl-4-phenylpyridinium (MPP<sup>+</sup>) treatment caused notable cell death in N2A neurons cocultured with activated BV2 cells in PM<sub>10</sub>-conditioned medium. Altogether, our results demonstrated that PM<sub>10</sub> plays a role in the neurodegeneration associated with PD. Thus, the impact of PM<sub>10</sub> on neurodegeneration could be related to detrimental air pollution-induced systemic effects on the brain.
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spelling doaj.art-0835479cd0e54a54a09615a685e6700d2023-11-23T17:01:36ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-06-012312648710.3390/ijms23126487Particulate Matter Exacerbates the Death of Dopaminergic Neurons in Parkinson’s Disease through an Inflammatory ResponseDabin Choi0Gaheon Lee1Kyung Hwa Kim2Hyunsu Bae3Department of Physiology, College of Korean Medicine, Kyung Hee University, 26-6 Kyungheedae-ro, Dongdaemoon-gu, Seoul 02453, KoreaDepartment of Health Sciences, The Graduate School of Dong-A University, 840 Hadan-dong, Saha-gu, Busan 49315, KoreaDepartment of Health Sciences, The Graduate School of Dong-A University, 840 Hadan-dong, Saha-gu, Busan 49315, KoreaDepartment of Physiology, College of Korean Medicine, Kyung Hee University, 26-6 Kyungheedae-ro, Dongdaemoon-gu, Seoul 02453, KoreaParticulate matter (PM), a component of air pollution, has been epidemiologically associated with a variety of diseases. Recent reports reveal that PM has detrimental effects on the brain. In this study, we aimed to investigate the biological effects of ambient particles on the neurodegenerative disease Parkinson’s disease (PD). We exposed mice to coarse particles (PM<sub>10</sub>: 2.5–10 μm) for short (5 days) and long (8 weeks) durations via intratracheal instillation. Long-term PM<sub>10</sub> exposure exacerbated motor impairment and dopaminergic neuron death in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse models. Short-term PM<sub>10</sub> exposure resulted in both pulmonary and systemic inflammatory responses in mice. We further investigated the mechanism underlying PM<sub>10</sub>-induced neurotoxicity in cocultures of lung LA-4 epithelial cells and RAW264.7 macrophages. PM<sub>10</sub> treatment elicited a dramatic increase in proinflammatory mediators in LA-4/RAW264.7 coculture. Treating BV2 microglial cells with PM<sub>10</sub>-treated conditioned medium induced microglial activation. Furthermore, 1-methyl-4-phenylpyridinium (MPP<sup>+</sup>) treatment caused notable cell death in N2A neurons cocultured with activated BV2 cells in PM<sub>10</sub>-conditioned medium. Altogether, our results demonstrated that PM<sub>10</sub> plays a role in the neurodegeneration associated with PD. Thus, the impact of PM<sub>10</sub> on neurodegeneration could be related to detrimental air pollution-induced systemic effects on the brain.https://www.mdpi.com/1422-0067/23/12/6487Parkinson’s diseaseparticulate matterneuroinflammationsystemic inflammationmicroglial activation
spellingShingle Dabin Choi
Gaheon Lee
Kyung Hwa Kim
Hyunsu Bae
Particulate Matter Exacerbates the Death of Dopaminergic Neurons in Parkinson’s Disease through an Inflammatory Response
International Journal of Molecular Sciences
Parkinson’s disease
particulate matter
neuroinflammation
systemic inflammation
microglial activation
title Particulate Matter Exacerbates the Death of Dopaminergic Neurons in Parkinson’s Disease through an Inflammatory Response
title_full Particulate Matter Exacerbates the Death of Dopaminergic Neurons in Parkinson’s Disease through an Inflammatory Response
title_fullStr Particulate Matter Exacerbates the Death of Dopaminergic Neurons in Parkinson’s Disease through an Inflammatory Response
title_full_unstemmed Particulate Matter Exacerbates the Death of Dopaminergic Neurons in Parkinson’s Disease through an Inflammatory Response
title_short Particulate Matter Exacerbates the Death of Dopaminergic Neurons in Parkinson’s Disease through an Inflammatory Response
title_sort particulate matter exacerbates the death of dopaminergic neurons in parkinson s disease through an inflammatory response
topic Parkinson’s disease
particulate matter
neuroinflammation
systemic inflammation
microglial activation
url https://www.mdpi.com/1422-0067/23/12/6487
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