Three month inhalation exposure to low-level PM2.5 induced brain toxicity in an Alzheimer's disease mouse model.

Although numerous epidemiological studies revealed an association between ambient fine particulate matter (PM2.5) exposure and Alzheimer's disease (AD), the PM2.5-induced neuron toxicity and associated mechanisms were not fully elucidated. The present study assessed brain toxicity in 6-month-ol...

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Autores principales: Sheng-Han Lee, Yi-Hsuan Chen, Chu-Chun Chien, Yuan-Horng Yan, Hsin-Chang Chen, Hsiao-Chi Chuang, Hui-I Hsieh, Kuan-Hung Cho, Li-Wei Kuo, Charles C-K Chou, Ming-Jang Chiu, Boon Lead Tee, Ta-Fu Chen, Tsun-Jen Cheng
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Publicado: Public Library of Science (PLoS) 2021
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Acceso en línea:https://doaj.org/article/3606c9a7715c4a5699389bc19bce8dbc
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spelling oai:doaj.org-article:3606c9a7715c4a5699389bc19bce8dbc2021-12-02T20:17:34ZThree month inhalation exposure to low-level PM2.5 induced brain toxicity in an Alzheimer's disease mouse model.1932-620310.1371/journal.pone.0254587https://doaj.org/article/3606c9a7715c4a5699389bc19bce8dbc2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0254587https://doaj.org/toc/1932-6203Although numerous epidemiological studies revealed an association between ambient fine particulate matter (PM2.5) exposure and Alzheimer's disease (AD), the PM2.5-induced neuron toxicity and associated mechanisms were not fully elucidated. The present study assessed brain toxicity in 6-month-old female triple-transgenic AD (3xTg-AD) mice following subchronic exposure to PM2.5 via an inhalation system. The treated mice were whole-bodily and continuously exposed to real-world PM2.5 for 3 months, while the control mice inhaled filtered air. Changes in cognitive and motor functions were evaluated using the Morris Water Maze and rotarod tests. Magnetic resonance imaging analysis was used to record gross brain volume alterations, and tissue staining with hematoxylin and eosin, Nissl, and immunohistochemistry methods were used to monitor pathological changes in microstructures after PM2.5 exposure. The levels of AD-related hallmarks and the oxidative stress biomarker malondialdehyde (MDA) were assessed using Western blot analysis and liquid chromatography-mass spectrometry, respectively. Our results showed that subchronic exposure to environmental levels of PM2.5 induced obvious neuronal loss in the cortex of exposed mice, but without significant impairment of cognitive and motor function. Increased levels of phosphorylated-tau and MDA were also observed in olfactory bulb or hippocampus after PM2.5 exposure, but no amyloid pathology was detected, as reported in previous studies. These results revealed that a relatively lower level of PM2.5 subchronic exposure from the environmental atmosphere still induced certain neurodegenerative changes in the brains of AD mice, especially in the olfactory bulb, entorhinal cortex and hippocampus, which is consistent with the nasal entry and spreading route for PM exposure. Systemic factors may also contribute to the neuronal toxicity. The effects of PM2.5 after a more prolonged exposure period are needed to establish a more comprehensive picture of the PM2.5-mediated development of AD.Sheng-Han LeeYi-Hsuan ChenChu-Chun ChienYuan-Horng YanHsin-Chang ChenHsiao-Chi ChuangHui-I HsiehKuan-Hung ChoLi-Wei KuoCharles C-K ChouMing-Jang ChiuBoon Lead TeeTa-Fu ChenTsun-Jen ChengPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 8, p e0254587 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Sheng-Han Lee
Yi-Hsuan Chen
Chu-Chun Chien
Yuan-Horng Yan
Hsin-Chang Chen
Hsiao-Chi Chuang
Hui-I Hsieh
Kuan-Hung Cho
Li-Wei Kuo
Charles C-K Chou
Ming-Jang Chiu
Boon Lead Tee
Ta-Fu Chen
Tsun-Jen Cheng
Three month inhalation exposure to low-level PM2.5 induced brain toxicity in an Alzheimer's disease mouse model.
description Although numerous epidemiological studies revealed an association between ambient fine particulate matter (PM2.5) exposure and Alzheimer's disease (AD), the PM2.5-induced neuron toxicity and associated mechanisms were not fully elucidated. The present study assessed brain toxicity in 6-month-old female triple-transgenic AD (3xTg-AD) mice following subchronic exposure to PM2.5 via an inhalation system. The treated mice were whole-bodily and continuously exposed to real-world PM2.5 for 3 months, while the control mice inhaled filtered air. Changes in cognitive and motor functions were evaluated using the Morris Water Maze and rotarod tests. Magnetic resonance imaging analysis was used to record gross brain volume alterations, and tissue staining with hematoxylin and eosin, Nissl, and immunohistochemistry methods were used to monitor pathological changes in microstructures after PM2.5 exposure. The levels of AD-related hallmarks and the oxidative stress biomarker malondialdehyde (MDA) were assessed using Western blot analysis and liquid chromatography-mass spectrometry, respectively. Our results showed that subchronic exposure to environmental levels of PM2.5 induced obvious neuronal loss in the cortex of exposed mice, but without significant impairment of cognitive and motor function. Increased levels of phosphorylated-tau and MDA were also observed in olfactory bulb or hippocampus after PM2.5 exposure, but no amyloid pathology was detected, as reported in previous studies. These results revealed that a relatively lower level of PM2.5 subchronic exposure from the environmental atmosphere still induced certain neurodegenerative changes in the brains of AD mice, especially in the olfactory bulb, entorhinal cortex and hippocampus, which is consistent with the nasal entry and spreading route for PM exposure. Systemic factors may also contribute to the neuronal toxicity. The effects of PM2.5 after a more prolonged exposure period are needed to establish a more comprehensive picture of the PM2.5-mediated development of AD.
format article
author Sheng-Han Lee
Yi-Hsuan Chen
Chu-Chun Chien
Yuan-Horng Yan
Hsin-Chang Chen
Hsiao-Chi Chuang
Hui-I Hsieh
Kuan-Hung Cho
Li-Wei Kuo
Charles C-K Chou
Ming-Jang Chiu
Boon Lead Tee
Ta-Fu Chen
Tsun-Jen Cheng
author_facet Sheng-Han Lee
Yi-Hsuan Chen
Chu-Chun Chien
Yuan-Horng Yan
Hsin-Chang Chen
Hsiao-Chi Chuang
Hui-I Hsieh
Kuan-Hung Cho
Li-Wei Kuo
Charles C-K Chou
Ming-Jang Chiu
Boon Lead Tee
Ta-Fu Chen
Tsun-Jen Cheng
author_sort Sheng-Han Lee
title Three month inhalation exposure to low-level PM2.5 induced brain toxicity in an Alzheimer's disease mouse model.
title_short Three month inhalation exposure to low-level PM2.5 induced brain toxicity in an Alzheimer's disease mouse model.
title_full Three month inhalation exposure to low-level PM2.5 induced brain toxicity in an Alzheimer's disease mouse model.
title_fullStr Three month inhalation exposure to low-level PM2.5 induced brain toxicity in an Alzheimer's disease mouse model.
title_full_unstemmed Three month inhalation exposure to low-level PM2.5 induced brain toxicity in an Alzheimer's disease mouse model.
title_sort three month inhalation exposure to low-level pm2.5 induced brain toxicity in an alzheimer's disease mouse model.
publisher Public Library of Science (PLoS)
publishDate 2021
url https://doaj.org/article/3606c9a7715c4a5699389bc19bce8dbc
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