Genomic Basis for Individual Differences in Susceptibility to the Neurotoxic Effects of Diesel Exhaust

Details

• Personal Author:
  Ashbrook DG ; Cormier SA ; Jones BC ; Lu L ; Menon SK ; Noël A ; O'Callaghan JP ; Penn AL ; Xu F ; Zhao W
• Description:
  Air pollution is a known environmental health hazard. A major source of air pollution includes diesel exhaust (DE). Initially, research on DE focused on respiratory morbidities; however, more recently, exposures to DE have been associated with neurological developmental disorders and neurodegeneration. In this study, we investigated the effects of sub-chronic inhalation exposure to DE on neuroinflammatory markers in two inbred mouse strains and both sexes, including whole transcriptome examination of the medial prefrontal cortex. We exposed aged male and female C57BL/6J (B6) and DBA/2J (D2) mice to DE, which was cooled and diluted with HEPA-filtered compressed air for 2 h per day, 5 days a week, for 4 weeks. Control animals were exposed to HEPA-filtered air on the same schedule as DE-exposed animals. The prefrontal cortex was harvested and analyzed for proinflammatory cytokine gene expression (Il1β, Il6, Tnfa) and transcriptome-wide response by RNA-seq. We observed differential cytokine gene expression between strains and sexes in the DE-exposed vs. control-exposed groups for Il1β, Tnfa, and Il6. For RNA-seq, we identified 150 differentially expressed genes between air and DE treatment related to natural killer cell-mediated cytotoxicity per Kyoto Encyclopedia of Genes and Genomes pathways. Overall, our data show differential strain-related effects of DE on neuroinflammation and neurotoxicity and demonstrate that B6 are more susceptible than D2 to gene expression changes due to DE exposures than D2. These results are important because B6 mice are often used as the default mouse model for DE studies and strain-related effects of DE neurotoxicity warrant expanded studies. [Description provided by NIOSH]
• Subjects:
  Air Pollution Animals Occupational Health Respiratory System Safety
• Keywords:
  Air Pollution Animal Studies Author Keywords: Diesel Exhaust Cytokines Diesel Exhaust Environmental Health Environmentally Persistent Free Radicals Gene Expression Inhalation Studies Neuroinflammation Neurological Reactions Neurophysiological Effects Neurotoxicity Pollution Sex Strain

  More +
• ISSN:
  1422-0067
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  Louisiana ; OSHA Region 3 ; OSHA Region 4 ; OSHA Region 6 ; Tennessee ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  23
• Issue:
  20
• NIOSHTIC Number:
  nn:20066239
• Citation:
  Int J Mol Sci 2022 Oct; 23(20):12461
• Contact Point Address:
  Alexandra Noël, Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA
• Email:
  anoel@lsu.edu
• Federal Fiscal Year:
  2023
• Peer Reviewed:
  True
• Source Full Name:
  International Journal of Molecular Sciences
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:9d8eae3b31dbc110562a22ae6a349b3aeb9ff1c232dd551bb0e529684380d65c986852bc484d488af2e2183a7b06c90096549587f19e6977342b5d4234bd2312
• Download URL:
  https://stacks.cdc.gov/view/cdc/212723/cdc_212723_DS1.pdf
• File Type:
  [PDF - 1.99 MB ]