title: A pilot study to assess effects of long-term inhalation of airborne particulate matter on early Alzheimer-like changes in the mouse brain.
abstract: Exposure to air pollutants, including particulate matter, results in activation of the brain inflammatory response and Alzheimer disease (AD)-like pathology in dogs and humans. However, the length of time required for inhalation of ambient particulate matter to influence brain inflammation and AD pathology is less clear. Here, we studied the effect of 3 and 9 months of air particulate matter (<2.5 μm diameter, PM2.5) exposure on brain inflammatory phenotype and pathological hallmarks of AD in C57BL/6 mice. Using western blot, ELISA, and cytokine array analysis we quantified brain APP, beta-site APP cleaving enzyme (BACE), oligomeric protein, total Aβ 1-40 and Aβ 1-42 levels, inducible nitric oxide synthase (iNOS), nitrotyrosine-modified proteins, HNE-Michael adducts, vascular cell adhesion molecule 1 (VCAM-1), glial markers (GFAP, Iba-1), pre- and post- synaptic markers (synaptophysin and PSD-95), cyclooxygenase (COX-1, COX-2) levels, and the cytokine profile in PM2.5 exposed and filtered air control mice. Only 9 month PM2.5 exposure increased BACE protein levels, APP processing, and Aβ 1-40 levels. This correlated with a concomitant increase in COX-1 and COX-2 protein levels and a modest alteration in the cytokine profile. These data support the hypothesis that prolonged exposure to airborne particulate matter has the potential to alter brain inflammatory phenotype and promote development of early AD-like pathology.
authors.affiliation: Department of Basic Sciences, UND School of Medicine and Health Sciences, Grand Forks, North Dakota, United States of America; Duke Molecular Physiology Institute, Duke University, Durham, North Carolina, United States of America.
authors.forename: Dhaval P
authors.initials: DP
authors.lastname: Bhatt
authors.affiliation: Department of Basic Sciences, UND School of Medicine and Health Sciences, Grand Forks, North Dakota, United States of America.
authors.forename: Kendra L
authors.initials: KL
authors.lastname: Puig
authors.affiliation: Dorothy M. Davis Heart and Lung Research Institute and Department of Physiology and Cell Biology, The Ohio State University College of Medicine, Columbus, Ohio, United States of America; College of Nursing, The Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Gorr
authors.affiliation: Dorothy M. Davis Heart and Lung Research Institute and Department of Physiology and Cell Biology, The Ohio State University College of Medicine, Columbus, Ohio, United States of America; College of Nursing, The Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Loren E
authors.initials: LE
authors.lastname: Wold
authors.affiliation: Department of Basic Sciences, UND School of Medicine and Health Sciences, Grand Forks, North Dakota, United States of America.
authors.forename: Colin K
authors.initials: CK
authors.lastname: Combs
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology*; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D016207:Cytokines / Q000378:metabolism; D019175:DNA Methylation; D000076122:Disks Large Homolog 4 Protein; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D051528:Guanylate Kinases / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D019570:Inhalation Exposure / Q000009:adverse effects*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008810:Mice, Inbred C57BL; D009457:Neuroglia / Q000378:metabolism; D015538:Nitrosation; D018384:Oxidative Stress; D052638:Particulate Matter / Q000009:adverse effects*; D010766:Phosphorylation; D010865:Pilot Projects; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; D015415:Biomarkers; D016207:Cytokines; D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; D005904:Glial Fibrillary Acidic Protein; D018836:Inflammation Mediators; D008565:Membrane Proteins; D052638:Particulate Matter; D019010:Vascular Cell Adhesion Molecule-1; D016875:tau Proteins; D011451:Prostaglandin-Endoperoxide Synthases; D051528:Guanylate Kinases; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509282:Bace1 protein, mouse