Genomic Basis for Individual Differences in Susceptibility to the Neurotoxic Effects of Diesel Exhaust
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 neurodegenerati...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/20/12461 |
| _version_ | 1797472743635025920 |
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| author | Alexandra Noël David G. Ashbrook Fuyi Xu Stephania A. Cormier Lu Lu James P. O’Callaghan Shyam K. Menon Wenyuan Zhao Arthur L. Penn Byron C. Jones |
| author_facet | Alexandra Noël David G. Ashbrook Fuyi Xu Stephania A. Cormier Lu Lu James P. O’Callaghan Shyam K. Menon Wenyuan Zhao Arthur L. Penn Byron C. Jones |
| author_sort | Alexandra Noël |
| collection | DOAJ |
| 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 (<i>Il1β</i>, <i>Il6</i>, <i>Tnfα</i>) 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 <i>Il1β</i>, <i>Tnfα</i>, and <i>Il6</i>. 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. |
| first_indexed | 2024-03-09T20:05:33Z |
| format | Article |
| id | doaj.art-2582620027c7477fa36c8d24065a3a05 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T20:05:33Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-2582620027c7477fa36c8d24065a3a052023-11-24T00:31:58ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-10-0123201246110.3390/ijms232012461Genomic Basis for Individual Differences in Susceptibility to the Neurotoxic Effects of Diesel ExhaustAlexandra Noël0David G. Ashbrook1Fuyi Xu2Stephania A. Cormier3Lu Lu4James P. O’Callaghan5Shyam K. Menon6Wenyuan Zhao7Arthur L. Penn8Byron C. Jones9Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USADepartment of Genetics, Genomics, and Informatics, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USADepartment of Genetics, Genomics, and Informatics, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USADepartment of Biological Sciences, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA 70808, USADepartment of Genetics, Genomics, and Informatics, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USAMolecular Neurotoxicology Laboratory, Toxicology, and Molecular Biology Branch, Health Effects Laboratory Division, Centers for Disease Control and Prevention, NIOSH, Morgantown, WV 26508, USADepartment of Mechanical and Industrial Engineering, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USADepartment of Genetics, Genomics, and Informatics, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USADepartment of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USADepartment of Genetics, Genomics, and Informatics, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USAAir 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 (<i>Il1β</i>, <i>Il6</i>, <i>Tnfα</i>) 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 <i>Il1β</i>, <i>Tnfα</i>, and <i>Il6</i>. 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.https://www.mdpi.com/1422-0067/23/20/12461diesel exhaustneurotoxicityneuroinflammationstrainsexpollution |
| spellingShingle | Alexandra Noël David G. Ashbrook Fuyi Xu Stephania A. Cormier Lu Lu James P. O’Callaghan Shyam K. Menon Wenyuan Zhao Arthur L. Penn Byron C. Jones Genomic Basis for Individual Differences in Susceptibility to the Neurotoxic Effects of Diesel Exhaust International Journal of Molecular Sciences diesel exhaust neurotoxicity neuroinflammation strain sex pollution |
| title | Genomic Basis for Individual Differences in Susceptibility to the Neurotoxic Effects of Diesel Exhaust |
| title_full | Genomic Basis for Individual Differences in Susceptibility to the Neurotoxic Effects of Diesel Exhaust |
| title_fullStr | Genomic Basis for Individual Differences in Susceptibility to the Neurotoxic Effects of Diesel Exhaust |
| title_full_unstemmed | Genomic Basis for Individual Differences in Susceptibility to the Neurotoxic Effects of Diesel Exhaust |
| title_short | Genomic Basis for Individual Differences in Susceptibility to the Neurotoxic Effects of Diesel Exhaust |
| title_sort | genomic basis for individual differences in susceptibility to the neurotoxic effects of diesel exhaust |
| topic | diesel exhaust neurotoxicity neuroinflammation strain sex pollution |
| url | https://www.mdpi.com/1422-0067/23/20/12461 |
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