Molecular Insights into PCB Neurotoxicity: Comparing Transcriptomic Responses across Dopaminergic Neurons, Population Blood Cells, and Parkinson's Disease Pathology
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE253569 | GEO | 2024/08/29
REPOSITORIES: GEO
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Project description:3,3’-Dichlorobiphenyl (PCB-11) is a non-legacy PCB congener widely detected in environmental samples and has been detected in human serum, but its toxicity potential is poorly understood. Zebrafish statically exposed to 4,500 µg/L PCB-11 at 24 hours post fertilization (hpf) were collected at 96 hpf for RNA sequencing.
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Project description:Exposure to Polychlorobiphenyls (PCBs) is known to cause serious health effects in human but the gene expression profiles leading to development of differnet diseases and disorders are not fully understood. The knowledge of global gene expression will help us to devlop early disease or disorder biomarkers for PCB induced health effects. We used microarrays to detail the global gene expression profile underlying the effects of PCB 138 exposure to human PBMC leading to identification of distinct classes of up-regulated and down-regulated genes and cellular processes. Keywords: PCB 138 Exposures
2011-04-19 | GSE22632 | GEO
Project description:Polychlorinated biphenyls (PCBs) are persistent environmental toxicants that pose a variety of health risks in humans. PCB 52 has been found in the indoor air of schools where adolescent students and staff are being actively exposed. This study examined the livers of adolescent Sprague-Dawley rats after sub-acute exposure to PCB 52 via nose-only inhalation. Rats were exposed for 4 hours daily for 28 consecutive days. RNA extracted from both male and female livers were submitted for RNA sequencing to compare the effects of PCB 52 on the expression of genes in the liver.
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Project description:Exposure to Polychlorobiphenyls (PCBs) is known to cause serious health effects in human but the gene expression profiles leading to development of differnet diseases and disorders are not fully understood. The knowledge of global gene expression will help us to devlop early disease or disorder biomarkers for PCB induced health effects. We used microarrays to detail the global gene expression profile underlying the effects of PCB 153 exposure to human PBMC leading to identification of distinct classes of up-regulated and down-regulated genes and cellular processes.
2011-04-19 | GSE22667 | GEO
Project description:Polychlorinated biphenyls (PCBs) are persistent environmental toxicants that pose a variety of health risks in humans. PCB 52 has been found in the indoor air of schools where adolescent students and staff are being actively exposed. This study examined the three different fat depots, namely, brown adipose tissue (BAT), subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT), of adolescent Sprague-Dawley rats after sub-acute exposure to PCB 52 via nose-only inhalation. Rats were exposed for 4 hours daily for 28 consecutive days. RNA extracted from both male and female fat depots were submitted for RNA sequencing to compare the effects of PCB 52 on the expression of genes in the fat depots.
2024-03-04 | GSE259369 | GEO
Project description:Polychlorinated biphenyls (PCBs) are persistent and ubiquitously distributed environmental pollutants. Based on their chemical structure, PCBs are classified into non-ortho substituted and ortho-substituted congeners. Non-ortho-substituted PCBs are structurally similar to dioxin or TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) and their mode of action and toxic effects are well established. In contrast, much less is known about the effects of ortho-substituted PCBs. Studies conducted so far have focused on tissue-specific effects but there is limited knowledge about the effects on the whole organism, particularly the sensitive developmental stages in vertebrates. Hence, in this study we investigated the effects of exposure to an environmentally relevant ortho-substituted PCB (2,2’,4,4’,5,5’-hexachlorobiphenyl; PCB153) on zebrafish embryos. We exposed zebrafish embryos to either DMSO (0.1%; solvent control) or three different concentrations of PCB153 (0.1, 1 and 10 μM) from 4 hours post-fertilization (hpf) to 120 hpf. At the end of the exposure, larvae were sampled for determining transcriptional changes (RNA sequencing) and the remaining embryos were maintained in contaminant-free environment. At 7 and 14 days post-fertilization (dpf), zebrafish larvae were assessed for locomotory behavior. We did not observe any overt phenotypes during the exposure period, but observed a spinal phenotype in the 10μM PCB153 treated group starting at 7 dpf. This phenotype was observed in a dose-dependent manner and majority of the embryos with this phenotype died by 14 dpf. RNA sequencing of 5 dpf larvae exposed to PCB153 also revealed dose-dependent changes in gene expression patterns. A total of 633, 2227, and 3378 differentially expressed genes were observed in 0.1, 1 and 10 μM PCB153 treated embryos, respectively. Among these, 301 genes were common to all treatment groups, and KEGG pathway analysis revealed enrichment of genes related to circadian rhythm, FOXO signaling and insulin resistance pathways. We are currently investigating the functions of genes that are uniquely altered by different PCB153 concentrations. Overall, these results suggest that developmental exposure to PCB153, a PCB congener highly prevalent in the environment, targets multiple physiological processes including photoperiod regulation and metabolism. [Funded by NIH P01ES021923 and NSF OCE-1314642].
2017-12-31 | GSE93310 | GEO
Project description:Exposure to Polychlorobiphenyls (PCBs) is known to cause serious health effects in human but the gene expression profiles leading to development of differnet diseases and disorders are not fully understood. The knowledge of global gene expression will help us to devlop early disease or disorder biomarkers for PCB induced health effects. We used microarrays to detail the global gene expression profile underlying the effects of PCB 138 exposure to human PBMC leading to identification of distinct classes of up-regulated and down-regulated genes and cellular processes. Keywords: PCB 138 Exposures PBMC cells are grown for 48 hours in RPMI 1640 supplemented with 10% FBS and 1X Pennicilllin-Streptromycin with 1.25 mircogram/ml PHA-M and 0.15% (v/v)pokeweed mitogen and 50 microgram Beta-mercaptoethanol.Trizol extraction of total RNA was performed according to the manufacturer's instructions. Biotinylated cRNA were prepared according to the standard Affymetrix protocol from 6 microgram of total RNA (Expression Analysis Technical Manual, 2001, Affymetrix). Following fragmentation, 10 microgram of cRNA were hybridized for 16 hr at 45C on GeneChip Human Genome Array (HGU133 plus 2.0). GeneChips were washed and stained in the Affymetrix Fluidics Station 450 and scanned using the Affymetrix GeneArray Scanner 3000. The data were analyzed with Microarray Suite version 5.0 (MAS 5.0) using Affymetrix default analysis settings and global scaling as normalization method. The trimmed mean target intensity of each array was arbitrarily set to 150.
2011-04-19 | E-GEOD-22632 | biostudies-arrayexpress
Project description:Exposure to Polychlorobiphenyls (PCBs) is known to cause serious health effects in human but the gene expression profiles leading to development of differnet diseases and disorders are not fully understood. The knowledge of global gene expression will help us to devlop early disease or disorder biomarkers for PCB induced health effects. We used microarrays to detail the global gene expression profile underlying the effects of PCB 153 exposure to human PBMC leading to identification of distinct classes of up-regulated and down-regulated genes and cellular processes. PBMC cells are grown for 48 hours in RPMI 1640 supplemented with 10% FBS and 1X Pennicilllin-Streptromycin with 1.25 mircogram/ml PHA-M and 0.15% (v/v)pokeweed mitogen and 50 microgram Beta-mercaptoethanol.Trizol extraction of total RNA was performed according to the manufacturer's instructions. Biotinylated cRNA were prepared according to the standard Affymetrix protocol from 6 microgram of total RNA (Expression Analysis Technical Manual, 2001, Affymetrix). Following fragmentation, 10 microgram of cRNA were hybridized for 16 hr at 45C on GeneChip Human Genome Array (HGU133 plus 2.0). GeneChips were washed and stained in the Affymetrix Fluidics Station 450 and scanned using the Affymetrix GeneArray Scanner 3000. The data were analyzed with Microarray Suite version 5.0 (MAS 5.0) using Affymetrix default analysis settings and global scaling as normalization method. The trimmed mean target intensity of each array was arbitrarily set to 150.
2011-04-19 | E-GEOD-22667 | biostudies-arrayexpress
Project description:Polychlorinated biphenyls (PCBs) are developmental neurotoxicants implicated as environmental risk factors for neurodevelopmental disorders (NDD). We examined the effects of prenatal exposure to a human-relevant mixture of PCBs on the DNA methylation profiles of fetal mouse brain and placenta. We found thousands of differentially methylated regions (DMRs) distinguishing placentas and brains from PCB-exposed embryos from sex-matched vehicle controls. In both placenta and brain, PCB-associated DMRs were enriched for functions related to neurodevelopment and cellular signaling and enriched within regions of bivalent chromatin. The placenta and brain PCB DMRs overlapped significantly and mapped to a shared subset of genes enriched for Wnt signaling, Slit/Robo signaling, and genes differentially expressed in NDD models. PBC DMRs also significantly overlapped with DMRs from the brains of humans with Rett syndrome and Dup15q syndrome. These results demonstrate that placenta can be used as a surrogate for embryonic brain DNA methylation changes relevant to an NDD.
2022-03-03 | GSE171017 | GEO
Project description:Polychlorinated biphenyls (PCBs) are developmental neurotoxicants implicated as environmental risk factors for neurodevelopmental disorders (NDD). We examined the effects of prenatal exposure to a human-relevant mixture of PCBs on the DNA methylation profiles of fetal mouse brain and placenta. We found thousands of differentially methylated regions (DMRs) distinguishing placentas and brains from PCB-exposed embryos from sex-matched vehicle controls. In both placenta and brain, PCB-associated DMRs were enriched for functions related to neurodevelopment and cellular signaling and enriched within regions of bivalent chromatin. The placenta and brain PCB DMRs overlapped significantly and mapped to a shared subset of genes enriched for Wnt signaling, Slit/Robo signaling, and genes differentially expressed in NDD models. PBC DMRs also significantly overlapped with DMRs from the brains of humans with Rett syndrome and Dup15q syndrome. These results demonstrate that placenta can be used as a surrogate for embryonic brain DNA methylation changes relevant to an NDD.
2022-03-03 | GSE171016 | GEO