title: Atypical microglial response to biodiesel exhaust in healthy and hypertensive rats.
abstract: Accumulating evidence suggests a deleterious role for urban air pollution in central nervous system (CNS) diseases and neurodevelopmental disorders. Microglia, the resident innate immune cells and sentinels in the brain, are a common source of neuroinflammation and are implicated in air pollution-induced CNS effects. While renewable energy, such as soy-based biofuel, is of increasing public interest, there is little information on how soy biofuel may affect the brain, especially in people with preexisting disease conditions. To address this, male spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) rats were exposed to 100% Soy-based Biodiesel Exhaust (100SBDE; 0, 50, 150 and 500μg/m3) by inhalation, 4h/day for 4 weeks (5 days/week). Ionized calcium-binding adapter molecule-1 (IBA-1) staining of microglia in the substantia nigra revealed significant changes in morphology with 100SBDE exposure in rats from both genotypes, where SHR were less sensitive. Aconitase activity was inhibited in the frontal cortex and cerebellum of WKY rats exposed to 100SBDE. No consistent changes occurred in pro-inflammatory cytokine expression, nitrated protein, or arginase1 expression in brain regions from either rat strain exposed to 100SBDE. However, while IBA-1 mRNA expression was not modified, CX3CR1 mRNA expression was lower in the striatum of 100SBDE exposed rats regardless of genotype, suggesting a downregulation of the fractalkine receptor on microglia in this brain region. Together, these data indicate that while microglia are detecting and responding to 100SBDE exposure with changes in morphology, there is reduced expression of CX3CR1 regardless of genetic background and the activation response is atypical without traditional inflammatory markers of M1 or M2 activation in the brain.
authors: Department of Anatomy and Cell Biology, The Stark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors: Christen L
authors: CL
authors: Mumaw
authors: Department of Biochemistry & Molecular Biology, Virginia Commonwealth University Medical Campus, Richmond, VA 23298, USA.
authors: Michael
authors: M
authors: Surace
authors: Department of Anatomy and Neurobiology, Virginia Commonwealth University Medical Campus, Richmond, VA 23298, USA.
authors: Shannon
authors: S
authors: Levesque
authors: Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, ORD, U.S. Environmental Protection Agency, Research Triangle Park, NC, 27711, USA.
authors: Urmila P
authors: UP
authors: Kodavanti
authors: Toxicity Assessment Division, National Health and Environmental Effects Research Laboratory, ORD, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
authors: Prasada Rao S
authors: PRS
authors: Kodavanti
authors: Integrated Systems Toxicology Division, National Health and Environmental Effects Research Laboratory, ORD, U.S. Environmental Protection Agency, Research Triangle Park, NC, 27711, USA.
authors: Joyce E
authors: JE
authors: Royland
authors: Department of Anatomy and Cell Biology, The Stark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA. Electronic address: mlblock@iupui.edu.
authors: Michelle L
authors: ML
authors: Block
mesh_terms: D000154:Aconitate Hydratase / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D056804:Biofuels / Q000633:toxicity*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D054428:Chemokine CX3CL1 / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism; D017628:Microglia / Q000145:classification / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013378:Substantia Nigra / Q000473:pathology*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D001335:Vehicle Emissions / Q000633:toxicity*
chemical_list: C100745:Aif1 protein, rat; D000975:Antioxidants; D056804:Biofuels; D002135:Calcium-Binding Proteins; D054428:Chemokine CX3CL1; D016207:Cytokines; D008840:Microfilament Proteins; D012333:RNA, Messenger; D001335:Vehicle Emissions; C002744:3-nitrotyrosine; D014443:Tyrosine; D014446:Tyrosine 3-Monooxygenase; D000154:Aconitate Hydratase
keywords: Air pollution; Atypical activation; Biodiesel; Brain; Microglia; Neurotoxicity