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Effects of 28-day nose-only inhalation of PCB52 (2,2′,5,5′-Tetrachlorobiphenyl) on the brain transcriptome

ABSTRACT: Banned from mass production, polychlorinated biphenyls (PCBs) still pose a neurological health threat decades later. PCB52, a volatile compound, has been found in the indoor air of schools where adolescent students and staff are exposed. The adolescent brain is vulnerable and highly influenced by the environment around it. This study used adolescent Sprague-Dawley rats to determine the neurological effects of a subacute (28-day) PCB52 inhalation exposure. Rats were exposed 4 h a day for 28 consecutive days with neurobehavioral tests conducted during the last 5 days of exposure. Based on the data including brain weights, PCB52 and metabolite levels, gene expression in the striatum and cerebellum, and neurobehavioral tests (Y-maze, HBT, OFT, and EPM); a subacute inhalation of PCB52 results in sex-specific differences in response to exposure. Our results indicate multilevel PCB52 influence that is different in adolescent males and females; from gene expression to downstream innate mechanisms driving behavior.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE246555 | GEO | 2024/11/08

REPOSITORIES: GEO

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Project description:Methylmercury (MeHg) is a ubiquitous environmental toxicant that is often detected in the tissues of fish-eating species. It has been well established that prenatal exposure to MeHg can lead to widespread brain damage and impaired neurological development resulting in defects ranging from severe cerebral palsy and cognitive deficits to impaired motor and sensory function. A wide range of environmental toxicants have been shown to induce transgenerational inheritance of diseases via changes in DNA methylation—a well-known epigenetic modification. Our previous research has demonstrated that developmental MeHg exposure may yield transgenerational inheritance of neurological dysfunction in adult F3-lineage zebrafish via quantitative neurobehavioral assays that evaluated the visual startle response, retinal electrophysiology, and locomotor function. The objective of the current study was to examine the correlation between neurobehavioral phenotypes and the transcriptome activity in the brain and retina of F3 zebrafish by RNA sequencing (RNAseq). Transcriptomic analyses of F3 generation MeHg-treated zebrafish (compared to control) revealed significant gene dysregulation in both the brain and retina. There were 1648 and 138 differentially expressed genes in the retina and brain, respectively (FDR <0.05). Thirty-five genes were commonly dysregulated in both organs. Gene set enrichment analysis revealed significantly enriched pathways including: neurodevelopment, visual functions, phototransduction, and motor movement. Moreover, commonly dysregulated genes were associated with circadian rhythm and metabolic pathways, as well as arginine and proline metabolism. To our knowledge, this is the first evidence of a transgenerational transcriptome induced by ancestral developmental exposure to MeHg in any species. If the transgenerational phenotypes, transcriptome, homologous biomarkers, or similar molecular pathways hold true for human populations, our findings have significant impact on global public health in terms of identifying the susceptible populations using biomarkers and preventing transgenerational inheritance of MeHg-induced neurobehavioral deficits.

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Effects of 28-day nose-only inhalation of PCB52 (2,2′,5,5′-Tetrachlorobiphenyl) on the brain transcriptome

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