Altered Genome-Wide Hippocampal Gene Expression Profiles Following Early Life Lead Exposure and their Potential for Reversal by Environmental Enrichment
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE180354 | GEO | 2022/07/31
REPOSITORIES: GEO
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Project description:This study focuses on the impact of developmental Pb exposure on splenic gene expression. Pb exposure from gestational day 8 (gd8) to post-natal day 21 (pnd21) was used to obtain insight into how Pb induces anemia and negatively influences the immune response Keywords: exposure analysis
2009-12-21 | GSE10312 | GEO
Project description:Lead (Pb2+) is an environmental contaminant that is widely distributed around the world, mainly due to anthropogenic sources. Developmental exposure to Pb2+ has been linked to neurodevelopmental impairments in different animal species. Studies have shown that developmental exposure to Pb2+ could interfere with normal gene expression patterns in the immature brain leading to neurodevelopmental neuropathologies. However, the precise molecular mechanisms underlying the neurotoxicity of developmental Pb2+ exposure are still to be elucidated. We used the fruit fly to gain insights into the molecular mechanisms affected by exposure to this neurotoxicant. The fruit fly, has been used recently to understand the behavioral, synaptic and molecular changes after developmental exposure to Pb+2. Our overarching hypothesis is that developmental exposure of the fruit fly to Pb+2 results in global gene expression dysregulation in the larval brain resulting in central nervous system developmental impairments. We collected RNA samples from larval brain of control and Pb2+-exposed flies and performed cRNA hybridization on a 4x44K Agilent microarray. Overall, Pb+2 results in transcriptional disturbances of important developmental signaling pathways in the larval brain.
2016-12-31 | GSE77417 | GEO
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
Project description:Heavy metal toxicity is a worldwide health problem. Lead exposure is of particular concern due to the adverse effects of low concentrations on cognitive development in children. Although the mechanism of lead neurotoxicity has been well studied, the analysis and molecular mechanism of the transgenerational effects of lead exposure-induced neurotoxicity are lacking. To address this, Drosophila, a powerful developmental animal model, was exposed to lead acetate. We found that Pb exposure during the developmental stage affected the neurodevelopment of F0 fruit flies, resulting in a loss of the correlation between the motor terminal area and muscle fiber area and the increased frequency of β-lobe midline crossing phenotype in Mushroom bodies. We also found that Pb exposure led to an increase in BRP expression, suggesting an increase in synaptic vesicle release sites and a decrease in synaptic vesicle protein SYN expression in F0 generation. This explained the results of our electrophysiological data that Pb exposure led to an increase in the amplitude of evoked excitatory junctional potential (EJP) and an increase in the frequency of spontaneous excitatory junctional potential (mEJP). Our results further confirmed that the developmental neurotoxicity of parental Pb exposure has a transgenerational effect. Neurodevelopmental defects, abnormalities in synaptic function, and repetitive behavior also were observed in the F3 offspring of F0 exposed to lead. Our Medip-seq analysis showed that Pb exposure altered the DNA methylation levels of many neurodevelopmentally associated genes (eg, hppy, nrg, baz, and spn) in the F3 offspring of the F0 generation with Pb exposure. Our findings suggest that epigenetic mechanisms may underlie the transgenerational inheritance of acquired phenotypic traits resulting from exposure to environmental factors.
2023-12-09 | GSE249281 | GEO
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
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 | GSE78879 | GEO
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 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. 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
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 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. 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-74038 | biostudies-arrayexpress
Project description:Plastic particles in water environment can adsorb heavy metals, leading to combined toxicity to aquatic organisms. However, current conclusions are mostly obtained based on cell population-average responses. Heterogeneity effects among cell populations in aquatic organisms remain unclear. This study analyzed the heterogeneity effects of 200 μg/L 100 nm polystyrene nanoplastics (PS-NPs), 50 μg/L lead (Pb), and their combined exposures on zebrafish intestine cells by single-cell RNA sequencing.A total of 38640 cells in the zebrafish intestine was obtained and identified as seven cell populations, including enterocytes, macrophages, neutrophils, B cells, T cells, enteroendocrine cells, and goblet cells.Co-exposure of PS-NPs and Pb caused similar transcriptome profiles with PS-NPs exposure in macrophages, which changed immunological recognition processes. The Pb exposure influenced the macrophages by direct cytotoxicity. However, the Pb alone and combined exposures induced similar modes of action in the enterocytes, including the generation of oxidative stress and abnormal lipid metabolism.
2022-02-25 | GSE165888 | GEO
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