Exposure of ultrafine particulate matter causes glutathione redox imbalance in the hippocampus: A neurometabolic susceptibility to Alzheimer's pathology

Soo Jin Park, Jimin Lee, Seunghoon Lee, Sangchul Lim, Juhwan Noh, So Yeon Cho, Junghee Ha, Hyunjeong Kim, Changsoo Kim, Sunho Park, Do Yup Lee, Eosu Kim

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27 Citations (Scopus)

Abstract

Particulate matter (PM) exposure is related to an increased risk of sporadic Alzheimer's disease (AD), the pathogenesis of which is explained by chronic neurometabolic disturbance. Therefore, PM-induced alterations in neurometabolism might herald AD. We aimed to identify brain region-specific changes in metabolic pathways associated with ultrafine particle (UFP) exposure and to determine whether such metabolic alterations are linked to susceptibility to AD. We constructed UFP exposure chambers and generated UFP by the pyrolysis method, which produces no toxic oxidized by-products of combustion, such as NOx and CO. Twenty male C57BL6 mice (11–12 months old) were exposed either to UFP or room air in the chambers for 3 weeks. One week following completion of UFP exposure, regional brain tissues, including the olfactory bulb, cortex, hippocampus, and cerebellum, were obtained and analyzed by metabolomics based on GC–MS and LC-MS, western blot analysis, and immunohistochemistry. Our results demonstrated that the metabolomic phenotype was distinct within the 4 different anatomical regions following UFP exposure. The highest level of metabolic change was identified in the hippocampus, a vulnerable region involved in AD pathogenesis. In this region, one of the key changes was perturbed redox homeostasis via alterations in the methionine-glutathione pathway. UFP exposure also induced oxidative stress and neuroinflammation, and importantly, increased Alzheimer's beta-amyloid levels in the hippocampus. These results suggest that inhaled UFP-induced perturbation in hippocampal redox homeostasis has a role in the pathogenesis of AD. Therefore, chronic exposure to UFP should be regarded as a cumulative environmental risk factor for sporadic AD.

Original languageEnglish
Article number137267
JournalScience of the Total Environment
Volume718
DOIs
Publication statusPublished - 2020 May 20

Bibliographical note

Publisher Copyright:
© 2020

All Science Journal Classification (ASJC) codes

  • Environmental Engineering
  • Environmental Chemistry
  • Waste Management and Disposal
  • Pollution

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