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Title: An Air Particulate Pollutant Induces Neuroinflammation and Neurodegeneration in Human Brain Models
Authors: Kang, You Jung
Tan, Hsih-Yin 
Lee, Charles Y.
Cho, Hansang
Keywords: astrocytes
human brain model
particulate matter
Issue Date: 24-Sep-2021
Publisher: John Wiley and Sons Inc
Citation: Kang, You Jung, Tan, Hsih-Yin, Lee, Charles Y., Cho, Hansang (2021-09-24). An Air Particulate Pollutant Induces Neuroinflammation and Neurodegeneration in Human Brain Models. Advanced Science 8 (21) : 2101251. ScholarBank@NUS Repository.
Rights: Attribution 4.0 International
Abstract: Fine particulate matter (PM2.5), a major component among air pollutants, highlights as a global health concern. Several epidemiological studies show the correlation between chronical PM2.5 exposure and incidents of neurological disorders including Alzheimer's disease. However, the mechanisms have not been well understood, partly due to the lack of model systems that reflect the physiologically relevant innate immunity in human brains. Here, PM2.5-polluted human brain models (PMBs) are created in a 3D microfluidic platform reconstituting key aspects of human brain immunity under the PM2.5 exposure. PM2.5 penetration across a blood–brain barrier (BBB) model and accumulation in the brain tissue side of the model are first validated. Second, the PMB model shows that the BBB-penetrating PM2.5 initiates astrogliosis, resulting in slight neuronal loss and microglial infiltration. Third, it is demonstrated that the infiltrating microglia obtain M1 phenotype induced by interleukin-1? and interferon-? from neurons and reactive astrocytes under the PM2.5 exposure. Finally, it is observed that additional proinflammatory mediators and nitric oxide released from the M1 microglia exacerbate neuronal damages, such as synaptic impairment, phosphoric tau accumulation, and neuronal death. This study suggests that PM2.5 can be a potential environmental risk factor for dementia mediated by the detrimental neuroinflammation. © 2021 The Authors. Advanced Science published by Wiley-VCH GmbH
Source Title: Advanced Science
ISSN: 2198-3844
DOI: 10.1002/advs.202101251
Rights: Attribution 4.0 International
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