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

Details

• Personal Author:
  Noël, Alexandra ; Ashbrook, David G. ; Xu, Fuyi ; Cormier, Stephania A. ; Lu, Lu ; O'Callaghan, James P. ; Menon, Shyam K. ; Penn, Arthur L. ; Jones, Byron C.
• 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 disorders and neurodegeneration. In this pilot study, we investigated the effects of sub-chronic inhalation exposure to DE on neuroinflammatory markers in two inbred mouse strains of 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 hours/day, 5 days/week, for 4 weeks. Control animals were exposed to HEPA-filtered air. The prefrontal cortex was harvested and analyzed for proinflammatory cytokine gene expression and transcriptome-wide response by RNA-sequencing. We observed differential cytokine gene expression between strains and sexes in the DE exposed vs. control-exposed groups for Il1b, Tnfa, and Il6. We identified 150 differentially expressed genes between air and DE groups which 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 B6are more susceptible than D2 to gene expression changes due to DE exposures. 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
  • Genomics
  • Occupational Health
  • Safety
  • Vehicle Emissions
• Keywords:
  • Air pollution
  • Exposure assessment
  • Diesel exhaust
  • Neurotoxicology
  • Inhalation
  • Gene expression
  • Cytotoxicity
  • Genomics
• Document Type:
  Text
• Genre:
  Abstract
• 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
• Pages in Document:
  2 pdf pages
• NIOSHTIC Number:
  nn:20071758
• Citation:
  13th International Particle Toxicology Conference, August 28-31, 2022, Santa Fe, New Mexico. Albuquerque, NM: University of New Mexico, 2022 Aug; :39
• Federal Fiscal Year:
  2022
• Peer Reviewed:
  False
• Download URL:
  https://stacks.cdc.gov/view/cdc/259983/cdc_259983_DS1.pdf
• File Type:
  [PDF - 666.39 KB]
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:4b4ced1b5d1f90a8f895adca4a8c3dc81b4f96da861a5c8d210fed512164d01be767caadb8577ed6be50c34a8fe1fb8ee1c9881597dd62ff0060443866fe7140