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Embryonic exposure to 100 µg/L lead results in sex-specific expression changes in genes associated with neurological system and cancer in the aged adult zebrafish brain [male]

ABSTRACT: Developmental lead (Pb) exposure has been linked to neurological health issues appearing in children. Results from non-human primate studies also suggest detrimental effects of an early life Pb exposure on neurological health, showing a pathological evidence of Alzheimer’s disease in the aged animal brain. To elucidate the impacts of a developmental Pb exposure on neurological health-related molecular changes occurring in the aged brain, aged zebrafish with a control treatment or an embryonic exposure to 100 µg/L Pb were subjected to a zebrafish-specific microarray analysis by sex. Gene ontology analysis showed alterations in distinct sets of genes associated with nervous system development and function in each sex. In aged adult female zebrafish, significant changes in expression profiles occurred in a number of genes involved in neurological disease and nervous system development and function. On the other hand, in aged adult males, a number of genes with significant expression alterations were found to be associated with cancer and tumors.

ORGANISM(S): Danio rerio

PROVIDER: GSE78879 | GEO | 2017/11/30

SECONDARY ACCESSION(S): PRJNA314271

REPOSITORIES: GEO

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Embryonic exposure to 100 µg/L lead results in sex-specific expression changes in genes associated with neurological system and cancer in the aged adult zebrafish brain [female]

Project description:Developmental lead (Pb) exposure has been linked to neurological health issues appearing in children. Results from non-human primate studies also suggest detrimental effects of an early life Pb exposure on neurological health, showing a pathological evidence of Alzheimer’s disease in the aged animal brain. To elucidate the impacts of a developmental Pb exposure on neurological health-related molecular changes occurring in the aged brain, aged zebrafish with a control treatment or an embryonic exposure to 100 µg/L Pb were subjected to a zebrafish-specific microarray analysis by sex. Gene ontology analysis showed alterations in distinct sets of genes associated with nervous system development and function in each sex. In aged adult female zebrafish, significant changes in expression profiles occurred in a number of genes involved in neurological disease and nervous system development and function. On the other hand, in aged adult males, a number of genes with significant expression alterations were found to be associated with cancer and tumors.

2017-11-30 | GSE78880 | GEO

Embryonic exposure to 10 µg/L lead results in male-specific expression changes in genes associated with nervous system development and function and Alzheimer’s disease in aged adult zebrafish brain

Project description:A developmental lead (Pb) exposure has been proposed as an environmental risk factor for adult neurodegenerative diseases including Alzheimer’s disease (AD). Recent animal studies showed pathological characteristics of AD in adults with a developmental Pb exposure, but additional studies are needed to investigate this phenomenon. To further assess the relationship between an embryonic Pb exposure and latent neurological alterations, the brain of adult female and male zebrafish aged 12 months that were exposed to a control treatment or 10 µg/L Pb only during embryogenesis (1- 72 hours after fertilization) were analyzed on a zebrafish-specific microarray platform. Gene ontology and pathway analysis revealed similarities in the top diseases and functional categories in both sexes, but females had 4.3 times more genes altered than males. In addition, alterations in genes associated with nervous system development and function were more pronounced with a set of 89 genes associated with AD including amyloid precursor protein (APP), apolipoprotein (APOE), and sortlin-related receptor precursor (SORL1) observed to be changed in adult females. Our observations suggest that an embryonic exposure to Pb at levels as low as 10 μg/L disturb global gene expression patterns in a sex-specific manner that could lead to neurological alterations in later life. With these findings, future studies investigating the adverse neurological outcomes of these changes in gene expression will facilitate our understanding of the impact of an embryonic 10 μg/L Pb exposure on neurological disease pathogenesis and the inclusion of additional concentrations will broaden our knowledge of dose-dependent changes.

2016-02-08 | GSE74038 | GEO

Embryonic exposure to 10 µg/L lead results in female-specific expression changes in genes associated with nervous system development and function and Alzheimer’s disease in aged adult zebrafish brain

2016-02-08 | GSE74037 | GEO

Embryonic exposure to 10 Âµg/L lead results in female-specific expression changes in genes associated with nervous system development and function and Alzheimerâs disease in aged adult zebrafish brain

Project description:A developmental lead (Pb) exposure has been proposed as an environmental risk factor for adult neurodegenerative diseases including Alzheimerâs disease (AD). Recent animal studies showed pathological characteristics of AD in adults with a developmental Pb exposure, but additional studies are needed to investigate this phenomenon. To further assess the relationship between an embryonic Pb exposure and latent neurological alterations, the brain of adult female and male zebrafish aged 12 months that were exposed to a control treatment or 10 Âµg/L Pb only during embryogenesis (1- 72 hours after fertilization) were analyzed on a zebrafish-specific microarray platform. Gene ontology and pathway analysis revealed similarities in the top diseases and functional categories in both sexes, but females had 4.3 times more genes altered than males. In addition, alterations in genes associated with nervous system development and function were more pronounced with a set of 89 genes associated with AD including amyloid precursor protein (APP), apolipoprotein (APOE), and sortlin-related receptor precursor (SORL1) observed to be changed in adult females. Our observations suggest that an embryonic exposure to Pb at levels as low as 10 Î¼g/L disturb global gene expression patterns in a sex-specific manner that could lead to neurological alterations in later life. With these findings, future studies investigating the adverse neurological outcomes of these changes in gene expression will facilitate our understanding of the impact of an embryonic 10 Î¼g/L Pb exposure on neurological disease pathogenesis and the inclusion of additional concentrations will broaden our knowledge of dose-dependent changes. A developmental exposure to 10ppb Pb induced global gene expression changes were analyzed in 12 months aged male and female zebarfish brains. A developmental exposure was done shortly after fertilization through 72 hours after fertilization.

2016-02-08 | E-GEOD-74037 | biostudies-arrayexpress

Embryonic exposure to 10 Âµg/L lead results in male-specific expression changes in genes associated with nervous system development and function and Alzheimerâs disease in aged adult zebrafish brain

2016-02-08 | E-GEOD-74038 | biostudies-arrayexpress

Global Gene Expression Analysis Reveals Dynamic and Developmental Stage–Dependent Enrichment of Lead-Induced Neurological Gene Alterations

Project description:Background: The underlying genetic mechanisms specific to subtle neurological alterations associated with environmental lead (Pb) exposures have not been clearly elucidated. Objectives: The goal of this study was to identify novel gene targets and the underlying genetic mechanisms associated with developmental Pb neurotoxicity. Methods: We first exposed zebrafish embryos to a range of Pb concentrations throughout early development to establish relative toxicity. Using the data from that experiment, we exposed another group of zebrafish embryos to a sublethal dose of Pb (100 ppb) immediately after fertilization through 72 or 120 hr postfertilization (hpf). Global gene expression was then analyzed for molecular pathways and gene ontology enrichment, and Western blot analysis was performed to investigate the translation of gene expression changes to protein levels. Results: After 72 hpf, we identified 231 probes representing 90 nonredundant genes with well-established function or orthology to human genes as being altered by Pb exposure. This gene set was both confirmatory and novel in nature and was highly enriched for neurological development, function, and disease. Moreover, gene changes at this time point were correlated to altered protein levels. Alternatively, the gene set at 120 hpf did not share association with neurological development. Conclusions: Global gene expression alterations associated with developmental Pb exposure were dynamic and dependent on developmental stage. Gene expression alterations at the 72‑hpf time point were highly enriched with genes and molecular pathways associated with neurological development and disease. Moreover, we identified a number of novel targets for future exploration

2018-07-20 | GSE117399 | GEO

Exposure to the heavy metal lead induces DNA copy number alterations in zebrafish cells

Project description:DNA copy number variants (CNVs) are associated with the development of complex neurological diseases and disorders including autism spectrum disorder, schizophrenia, Alzheimer’s disease, and Parkinson’s disease. Exposure to multiple environmental chemicals including various heavy metals is suggested as a risk factor in these neurological diseases and disorders, but few studies have addressed if heavy metal exposure can result in spontaneous DNA copy number changes as a genetic mechanism contributing to these disease outcomes. In this study to further investigate the relationship between heavy metal exposure and spontaneous copy number alterations (CNAs), zebrafish fibroblast cells were exposed to the neurotoxicant lead (Pb). A crystal violet assay was first used to determine exposure concentrations with greater than 80% cell confluency. Then a zebrafish-specific array comparative genomic hybridization (CGH) platform was used to detect CNAs following a 72 hour Pb exposure (0.24, 2.4, or 24 μM). The Pb exposure resulted in 72 CNA amplifications ranging in size from 5 to 329 kb. No deletions were detected. CNAs resulted in 15 copy number alteration regions (CNARs), leaving 7 singlet CNAs. Two of the singlets were within high repeat genomic locations. The number of CNAs tended to increase in a concentration dependent manner. Several CNARs encompassed genes previously reported to have altered expression with Pb exposure, suggesting a mechanistic link. In addition, almost all genes are associated within a molecular network with the amyloid precursor protein (APP). Overall, these findings show that Pb exposure results in spontaneous CNAs that could serve as a mechanism driving adverse health outcomes associated with Pb toxicity including neurological disease pathogenesis for further study.

2020-12-01 | GSE149382 | GEO

Zebrafish Metabolomics: Model for Environmental Metal Toxicity

Project description:This metabolomics seed project will test the hypothesis that zebrafish can provide mechanistic insights into the human health effects of developmental exposure to Cd and Pb. We will use broad spectrum metabolomics of zebrafish larvae after exposure to Cd, Pb, and Cd and Pb compared to controls. Activity observed at 5 days post fertilization is will be used to determine if there is a correlation between biological pathways implicated by these metabolic profiles and cardiovascular, metabolic (obesity), and neurological phenotypes. The behavioral phenotypes have been quantified in zebrafish previously and have been measured in the Newborn Epigenetic STudy (NEST), a NIH-funded project that is investigating how environmental exposures and nutrition, in the womb and during childhood, affect how genes work and how these exposures developed into obesity and other diseases, disorders, and conditions. The results from this study will demonstrate the power of using zebrafish as a model for mechanism discovery in exposure using metabolomics to advance understanding of early life exposure to Cd and Pb and serve as preliminary data for opportunities.

2016-03-09 | ST000365 | MetabolomicsWorkbench

Embryonic exposure to 100 µg/L lead results in sex-specific expression changes in genes associated with neurological system and cancer in the aged adult zebrafish brain

Project description:Embryonic exposure to 100 µg/L lead results in sex-specific expression changes in genes associated with neurological system and cancer in the aged adult zebrafish brain

| PRJNA314269 | ENA

Hippocampal methylome of rats exposed to lead at different developmental stages

Project description:Developmental lead (Pb) exposure results in persistent cognitive/behavioral impairments as well as an elevated risk for developing a variety of diseases in later life. Environmental exposures during development can result in a variety of epigenetic changes, including alterations in DNA methylation, that can influence gene expression patterns and affect the function and development of the nervous system. The present promoter-based methylation microarray profiling study explored the extent to which developmental Pb exposure may modify the methylome of a brain region, hippocampus, known to be sensitive to the effects of Pb exposure. Male and female Long Evans rats were exposed to 0 ppm, 150 ppm, 375 ppm, or 750 ppm Pb through perinatal exposures (gestation through lactation), early postnatal exposures (birth through weaning), or long-term postnatal exposures (birth through postnatal day 55). Results showed a significant contribution of sex to the hippocampal methylome and effects of Pb exposure level, with non-linear dose response effects on methylation. Surprisingly, the developmental period of exposure contributed only a small amount of variance to the overall data and gene ontology (GO) analysis revealed the largest number of overrepresented GO terms in the groups with the lowest level of exposure. The highest number of significant differentially methylated regions was found in females exposed to Pb at the lowest exposure level. Our data reinforce the significant effect that low level Pb exposure may have on gene-specific DNA methylation patterns in brain and that this occurs in a sex-dependent manner. NimbleGen Rat CpG Island plus RefSeq Promoter 720k array

2018-10-30 | GSE106323 | GEO

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