Hippocampal methylome of rats exposed to lead at different developmental stages
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PROVIDER: PRJNA416305 | ENA |
REPOSITORIES: ENA
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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: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: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)
2012-05-31 | GSE38348 | GEO
Project description:The experiment was designed to investigate the regulatory landscape of H3K27me3, a histone methylation form, in the hippocampal neurons upon lead exposure. It reveals that the targeting pathways were altered and migrated throughout the genome, indicating that H3K27me3's sophisticated alterations are responsible for lead-led impairment of hippocampal neurons. Besides, the causes leading to its adaptive changes were figured out.
2018-11-17 | E-MTAB-6837 | biostudies-arrayexpress
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: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.
| S-EPMC5952363 | biostudies-literature
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)
2014-04-10 | GSE56666 | GEO
Project description:BackgroundA complete explanation of the mechanisms by which Pb2+ exerts toxic effects on developmental central nervous system remains unknown. Glutamate is critical to the developing brain through various subtypes of ionotropic or metabotropic glutamate receptors (mGluRs). Ionotropic N-methyl-D-aspartate receptors have been considered as a principal target in lead-induced neurotoxicity. The relationship between mGluR3/mGluR7 and synaptic plasticity had been verified by many recent studies. The present study aimed to examine the role of mGluR3/mGluR7 in lead-induced neurotoxicity.MethodsTwenty-four adult and female rats were randomly selected and placed on control or 0.2% lead acetate during gestation and lactation. Blood lead and hippocampal lead levels of pups were analyzed at weaning to evaluate the actual lead content at the end of the exposure. Impairments of short -term memory and long-term memory of pups were assessed by tests using Morris water maze and by detection of hippocampal ultrastructural alterations on electron microscopy. The impact of lead exposure on mGluR3 and mGluR7 mRNA expression in hippocampal tissue of pups were investigated by quantitative real-time polymerase chain reaction and its potential role in lead neurotoxicity were discussed.ResultsLead levels of blood and hippocampi in the lead-exposed rats were significantly higher than those in the controls (P < 0.001). In tests using Morris Water Maze, the overall decrease in goal latency and swimming distance was taken to indicate that controls had shorter latencies and distance than lead-exposed rats (P = 0.001 and P < 0.001 by repeated-measures analysis of variance). On transmission electron microscopy neuronal ultrastructural alterations were observed and the results of real-time polymerase chain reaction showed that exposure to 0.2% lead acetate did not substantially change gene expression of mGluR3 and mGluR7 mRNA compared with controls.ConclusionExposure to lead before and after birth can damage short-term and long-term memory ability of young rats and hippocampal ultrastructure. However, the current study does not provide evidence that the expression of rat hippocampal mGluR3 and mGluR7 can be altered by systemic administration of lead during gestation and lactation, which are informative for the field of lead-induced developmental neurotoxicity noting that it seems not to be worthwhile to include mGluR3 and mGluR7 in future studies.
| S-EPMC2674876 | biostudies-literature
Project description:Study the effect of fetal alcohol exposure (FAE) on hippocampal development Compare the pattern of gene expression in the hippocampus of FAE and control rats fed either an isocaloric diet or a normal diet, at post-natal day 5 of development. FAE will delay the maturation of the hippocampus Rats were fed one of three diet, a liquid diet with 5% ethanol (FAE group), an isocaloric liquid diet (Isocalorc group) or nomal lab chao (normal group) Keywords: dose response
2004-11-24 | GSE1997 | GEO
Project description:Developmental lead (Pb) exposure has profound effects on cognition and behavior. Much is known about effects of Pb on hippocampal-mediated behaviors, but little is known about the molecular consequences of Pb exposure and the influences of developmental timing of exposure, level of exposure, and sex as effect modifiers of Pb exposure on the brain. The aim of this study was to examine the effects of different levels of Pb exposure (250 and 750 ppm Pb acetate) during perinatal (gestation/lactation) and postnatal (through postnatal day 45) periods on the hippocampal transcriptome in male and female Long Evans rats. Total RNA was extracted from hippocampus from four animals per experimental condition. RNA was hybridized to Affymetrix Rat Gene RNA Arrays using standard methods. Pb exposure per se influenced the expression of 717 transcripts (328 unique annotated genes), with many influenced in a sex-independent manner. Significant differences in gene expression patterns were also influenced by timing and level of exposure, with generally larger effects at the lower level of exposure across all groups. Statistically enriched biological functions included ion binding, regulation of RNA metabolic processes, and positive regulation of macromolecule biosynthetic processes. Processes of regulation of transcription and regulation of gene expression were preferentially enriched in males, regardless of timing or amount of Pb exposure. The effect on transcription factors and the diverse pathways or networks affected by Pb suggest a substantial effect of developmental Pb exposure on plasticity and adaptability, with these effects significantly modified by sex, developmental window of exposure, and level of Pb exposure.
| S-EPMC3499078 | biostudies-literature