Mapping the effects of developmental lead (Pb) exposure on the hippocampus with single cell analysis
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PROVIDER: PRJNA637046 | ENA |
REPOSITORIES: ENA
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Project description:Lead (Pb) exposure is ubiquitous with permanent neurodevelopmental effects. The hippocampus brain region is involved in learning and memory with heterogeneous cellular composition. The hippocampus cell type-specific responses to Pb are unknown. This experiement sought to examine perinatal Pb treatment effects on adult hippocampus gene expression, at the level of individual cells. In mice perinatally exposed to control water or a human physiologically-relevant level (32 ppm in maternal drinking water) of Pb, two weeks prior to mating through weaning, we tested for hippocampus gene expression and cellular differences at 5-months of age.
2020-06-04 | GSE151723 | 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:In this study we analyzed the effects of lead-exposure up hippocampal gene expression in males and females exposed to 0ppm, 250ppm and 750ppm lead during two different developmental periods, perinatal (in utero through to weaning at PND21) and postnatal (PND0-PND45). All tissue was taken at PND 55. We used affymetrix Rat Gene 1.0ST arrays to obtain global gene expression data from each animal, with a group size of 4 for all conditions (Total number of Arrays = 40) Gene expression was profiled in hippocampus at no lead exposure (0ppm), 250ppm and 750 ppm lead exposure level at peinatal and postnaltal developmental period.
2012-05-30 | E-GEOD-38348 | biostudies-arrayexpress
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: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. The quality of the environment can modify negative influences from Pb exposure. How the interaction between Pb and quality of the environment influences gene expression pattern in the brain affecting the development treajectory is unexplored. We used RNA-seq to examine how the interaction between developmental Pb exposure and living in an enriched versus a non-enriched environment affects genome-wide gene expression pattern in Hippocampus (HIPP) CA1.
2022-07-31 | GSE180354 | GEO
Project description:Lead (Pb) exposure is associated with a wide range of neurological deficits. Epigenetic changes, such as DNA methylation, may be impacted by environmental exposures and can affect neurodevelopmental outcomes over the life-course. Mating mice were obtained from a C57BL/6J background agouti Avy strain. Virgin dams (a/a) were randomly assigned exposure to 2.1 ppm (low) or 32 ppm (high) Pb-acetate through the drinking water, started two weeks prior to mating with viable yellow agouti male mice (Avy/a) and continued throughout gestation and three weeks after birth. At 10 months of age, we separated brain NeuN+ (a marker for neuronal nuclei) neuronal nuclei from NeuN non-neuronal nuclei in mice. We investigated neuron specific genome-wide promoter DNA methylation associated with early-life Pb exposures using the Roche NimbleGen Mouse DNA methylation 3x720K CpG island Promoter Array.
2019-04-12 | GSE125174 | 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:The developing epigenome changes rapidly, potentially making it more sensitive to toxicant exposures. DNA modifications, including methylation and hydroxymethylation, are important parts of the epigenome that may be affected by environmental exposures. However, most studies do not differentiate between these two DNA modifications, possibly masking significant effects. To investigate the relationship between DNA hydroxymethylation and developmental exposure to common contaminants, a collaborative, NIEHS-sponsored consortium, TaRGET II, initiated longitudinal mouse studies of developmental exposure to human-relevant levels of the phthalate plasticizer di(2-ethylhexyl) phthalate (DEHP), and the metal lead (Pb). Exposures to 25 mg DEHP/kg of food (approximately 5 mg DEHP/kg body weight) or 32 ppm Pb-acetate in drinking water were administered to nulliparous adult female mice. Exposure began 2 weeks before breeding, and continued throughout pregnancy and lactation, until offspring were 21 days old. At 5 months, perinatally exposed offspring blood and cortex tissue were collected, for a total of 25 male mice and 17 female mice (n=5-7 per tissue and exposure). DNA was extracted and hydroxymethylation was measured using hydroxymethylated DNA immunoprecipitation sequencing (hMeDIP-seq). Differential peak and pathway analysis was conducted comparing across exposure groups, tissue types, and animal sex, using an FDR cutoff of 0.15. DEHP-exposed females had two genomic regions with lower hydroxymethylation in blood and no differences in cortex hydroxymethylation. For DEHP-exposed males, ten regions in blood (six higher and four lower) and 246 regions (242 higher and four lower) and four pathways in cortex were identified. Pb-exposed females had no statistically significant differences in blood or cortex hydroxymethylation compared to controls. Pb-exposed males, however, had 385 regions (all higher) and six pathways altered in cortex, but no differential hydroxymethylation was identified in blood. Overall, perinatal exposure to human-relevant levels of two common toxicants showed differences in DNA hydroxymethylation specific to sex, exposure type, and tissue, but male cortex was most susceptible to hydroxymethylation differences by exposure. Future assessments should focus on understanding if these findings indicate potential biomarkers of exposure or are related to functional long-term health effects.
2023-04-28 | GSE229717 | GEO
Project description:In this study we analyzed the effects of lead-exposure up hippocampal gene expression in males and females exposed to 0ppm, 250ppm and 750ppm lead during two different developmental periods, perinatal (in utero through to weaning at PND21) and postnatal (PND0-PND45), across three strains (Fischer, Long Evans and Sprague Dawley). All tissue was taken at PND 55. We used affymetrix Rat Gene 1.0ST arrays to obtain global gene expression data from each animal, with a group size of 4 for all conditions (Total number of Arrays = 119) Gene expression was profiled in the hippocampus of rats at no lead exposure (0ppm), 250ppm and 750 ppm lead exposure levels during perinatal and postnatal developmental periods of both males and females of three strains of rat (Fischer, Long Evans and Sprague Dawley).
2014-04-10 | E-GEOD-56666 | biostudies-arrayexpress
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