title: Microglial priming through the lung-brain axis: the role of air pollution-induced circulating factors.
abstract: Air pollution is implicated in neurodegenerative disease risk and progression and in microglial activation, but the mechanisms are unknown. In this study, microglia remained activated 24 h after ozone (O3) exposure in rats, suggesting a persistent signal from lung to brain. Ex vivo analysis of serum from O3-treated rats revealed an augmented microglial proinflammatory response and β-amyloid 42 (Aβ42) neurotoxicity independent of traditional circulating cytokines, where macrophage-1 antigen-mediated microglia proinflammatory priming. Aged mice exhibited reduced pulmonary immune profiles and the most pronounced neuroinflammation and microglial activation in response to mixed vehicle emissions. Consistent with this premise, cluster of differentiation 36 (CD36)(-/-) mice exhibited impaired pulmonary immune responses concurrent with augmented neuroinflammation and microglial activation in response to O3 Further, aging glia were more sensitive to the proinflammatory effects of O3 serum. Together, these findings outline the lung-brain axis, where air pollutant exposures result in circulating, cytokine-independent signals present in serum that elevate the brain proinflammatory milieu, which is linked to the pulmonary response and is further augmented with age.-Mumaw, C. L., Levesque, S., McGraw, C., Robertson, S., Lucas, S., Stafflinger, J. E., Campen, M. J., Hall, P., Norenberg, J. P., Anderson, T., Lund, A. K., McDonald, J. D., Ottens, A. K., Block, M. L. Microglial priming through the lung-brain axis: the role of air pollution-induced circulating factors.
authors: Department of Anatomy and Cell Biology, The Stark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, Indiana, USA;
authors: Christen L
authors: CL
authors: Mumaw
authors: Department of Anatomy and Neurobiology, Virginia Commonwealth University Medical Campus, Richmond, Virginia, USA;
authors: Shannon
authors: S
authors: Levesque
authors: Department of Anatomy and Neurobiology, Virginia Commonwealth University Medical Campus, Richmond, Virginia, USA;
authors: Constance
authors: C
authors: McGraw
authors: Department of Pharmaceutical Sciences and.
authors: Sarah
authors: S
authors: Robertson
authors: Department of Pharmaceutical Sciences and.
authors: Selita
authors: S
authors: Lucas
authors: Department of Anatomy and Neurobiology, Virginia Commonwealth University Medical Campus, Richmond, Virginia, USA;
authors: Jillian E
authors: JE
authors: Stafflinger
authors: Department of Pharmaceutical Sciences and.
authors: Matthew J
authors: MJ
authors: Campen
authors: Department of Pharmaceutical Sciences and.
authors: Pamela
authors: P
authors: Hall
authors: Radiopharmaceutical Sciences, Keck-University of New Mexico Small-Animal Imaging Resource, College of Pharmacy, University of New Mexico, Albuquerque, New Mexico, USA;
authors: Jeffrey P
authors: JP
authors: Norenberg
authors: Radiopharmaceutical Sciences, Keck-University of New Mexico Small-Animal Imaging Resource, College of Pharmacy, University of New Mexico, Albuquerque, New Mexico, USA;
authors: Tamara
authors: T
authors: Anderson
authors: Department of Biological Sciences, Advanced Environmental Research Institute, University of North Texas, Denton, Texas, USA; and.
authors: Amie K
authors: AK
authors: Lund
authors: Lovelace Respiratory Research Institute, Albuquerque, New Mexico, USA.
authors: Jacob D
authors: JD
authors: McDonald
authors: Department of Anatomy and Neurobiology, Virginia Commonwealth University Medical Campus, Richmond, Virginia, USA;
authors: Andrew K
authors: AK
authors: Ottens
authors: Department of Anatomy and Cell Biology, The Stark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, Indiana, USA; mlblock@iupui.edu.
authors: Michelle L
authors: ML
authors: Block
mesh_terms: D000397:Air Pollution / Q000009:adverse effects*; D000818:Animals; D000906:Antibodies; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002460:Cell Line; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008171:Lung Diseases / Q000139:chemically induced* / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000276:immunology; D051379:Mice; D017628:Microglia / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010126:Ozone / Q000633:toxicity*; D051381:Rats
chemical_list: D000906:Antibodies; D016177:Macrophage-1 Antigen; D010126:Ozone
keywords: glia; inhaled pollutants; neuroinflammation