Journal article
Interactions of Polychlorinated Biphenyls and Their Metabolites with the Brain and Liver Transcriptome of Female Mice
ACS chemical neuroscience, Vol.15(21), pp.3991-4009
10/11/2024
DOI: 10.1021/acschemneuro.4c00367
PMCID: PMC11587508
PMID: 39392776
Appears in UI Libraries Support Open Access
Abstract
Exposure to polychlorinated biphenyls (PCBs) is linked to neurotoxic effects. This study aims to close knowledge gaps regarding the specific modes of action of PCBs in female C57BL/6J mice (>6 weeks) orally exposed for 7 weeks to a human-relevant PCB mixture (MARBLES mix) at 0, 0.1, 1, and 6 mg/kg body weight/day. PCB and hydroxylated PCB (OH-PCBs) levels were quantified in the brain, liver, and serum; RNA sequencing was performed in the striatum, prefrontal cortex, and liver, and metabolomic analyses were performed in the striatum. Profiles of PCBs but not their hydroxylated metabolites were similar in all tissues. In the prefrontal cortex, PCB exposure activated the oxidative phosphorylation respiration pathways, while suppressing the axon guidance pathway. PCB exposure significantly changed the expression of genes associated with neurodevelopmental and neurodegenerative diseases in the striatum, impacting pathways like growth hormone synthesis and dendrite development. PCBs did not affect the striatal metabolome. In contrast to the liver, which showed activation of metabolic processes following PCB exposure and the induction of cytochrome P450 enzymes, the expression of xenobiotic processing genes was not altered by PCB exposure in either brain region. Network analysis revealed complex interactions between individual PCBs (e.g., PCB28 [2,4,4'-trichlorobiphenyl]) and their hydroxylated metabolites and specific differentially expressed genes (DEGs), underscoring the need to characterize the association between specific PCBs and DEGs. These findings enhance the understanding of PCB neurotoxic mechanisms and their potential implications for human health.
Details
- Title: Subtitle
- Interactions of Polychlorinated Biphenyls and Their Metabolites with the Brain and Liver Transcriptome of Female Mice
- Creators
- Amanda J Bullert - University of IowaHui Wang - University of IowaAnthony E Valenzuela - University of California, DavisKari Neier - University of California Davis Medical CenterRebecca J Wilson - University of California, DavisJessie R Badley - University of California, DavisJanine M LaSalle - University of California, DavisXin Hu - Emory UniversityPamela J Lein - University of California, DavisHans-Joachim Lehmler - Interdisciplinary Graduate Program in Human Toxicology, University of Iowa, Iowa City, Iowa 52242, United States
- Resource Type
- Journal article
- Publication Details
- ACS chemical neuroscience, Vol.15(21), pp.3991-4009
- DOI
- 10.1021/acschemneuro.4c00367
- PMID
- 39392776
- PMCID
- PMC11587508
- NLM abbreviation
- ACS Chem Neurosci
- ISSN
- 1948-7193
- eISSN
- 1948-7193
- Publisher
- American Chemical Society
- Grant note
- National Institute of Environmental Health Sciences of the National Institutes of Health: R01ES014901, R01ES029213, R01ES031098 Environmental Health Sciences Research Center at UC Davis: NIH P30 ES023513 University of Iowa: NIH P30 ES005605 Iowa Superfund Research Program: NIH P42 ES013661
This work wassupported by grants R01ES014901, R01ES029213, and R01ES031098 from the National Institute of Environmental Health Sciences of the National Institutes of Health and conducted in part in laboratory facilities supported by the Environmental Health Sciences Research Center at UC Davis (NIH P30 ES023513) and the University of Iowa (NIH P30 ES005605),as well as the Iowa Superfund Research Program (NIH P42 ES013661).The content is solely the responsibility of the authors and does notnecessarily represent the official views of the funding agencies listed above.
- Language
- English
- Date published
- 10/11/2024
- Academic Unit
- Occupational and Environmental Health; Iowa Neuroscience Institute; Iowa Superfund Research Program
- Record Identifier
- 9984723059902771
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