Embryonic exposure to 10 µg/L lead results in sex-specific expression changes in aged adult zebrafish brain
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ABSTRACT:
ORGANISM(S): Danio rerio
SUBMITTER: Jinyoung Lee
PROVIDER: E-GEOD-74039 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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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:The zebrafish (Danio rerio) is a popular animal model in studies of vertebrate development and organogenesis. Recent research has shown a similarity of approximately 70% between the human and zebrafish genomes and of 84% in human disease-causing genes, specifically. Zebrafish embryos have a number of desirable features, including transparency, a large size, and rapid embryogenesis. Protein phosphorylation is a well-known post-translational modification (PTM), which performs various biological functions. Recent mass spectrometry (MS) developments have enabled the study of global phosphorylation patterns by using MS-based proteomics coupled with TiO2 phosphopeptide enrichment. In the present study, we identified 3,500 non-redundant phosphorylation sites on 2,166 phosphoproteins and 1,564 quantified phosphoproteins in zebrafish embryos.
2015-10-14 | PXD002232 | Pride
Project description:Mass spectrometry (MS)-based top-down proteomics (TDP) delineates proteoforms in cells and requires high-resolution proteoform separation. Herein, for the first time, we employed an automated capillary isoelectric focusing-tandem MS (cIEF-MS/MS) system for large-scale TDP of complex proteomes. Single-shot cIEF-MS/MS identified 771 proteoforms from an Escherichia coli (E. coli) proteome consuming only nanograms of proteins. Coupling two-dimensional size exclusion chromatography (SEC)-cIEF, named “gel-free 2D-PAGE”, to ESI-MS/MS enabled the identification of nearly 2000 proteoforms from the E. coli proteome. Label-free quantitative TDP of zebrafish male and female brains using the SEC-cIEF-MS/MS quantified thousands of proteoforms and revealed sex-dependent proteoform profiles in brains. We discovered several proteolytic proteoforms of pro-opiomelanocortin and prodynorphin with significantly higher abundance in male brains as potential endogenous hormone proteoforms. Multi-level quantitative proteomic analyses (TDP and bottom-up proteomics (BUP)) of the brains revealed that majority of proteoforms having statistically significant difference in abundance between genders (TDP) showed no abundance difference at the corresponding protein group level (BUP), which highlights the importance of delineating proteins in a proteoform-specific manner for accurately understanding protein function.
2020-12-08 | PXD020342 | Pride
Project description:Sorafenib is associated with cardiac adverse effects, including left ventricular dysfunction. However, the precise mechanism remains unclear. Here, we aimed to establish the genes responsible for this cardiotoxicity using zebrafish. A pigmentless zebrafish line expressing green fluorescent protein in the heart were treated with or without sorafenib. In vivo fluorescent cardiac imaging revealed that the ventricular dimension of the longitudinal axis in zebrafish treated with sorafenib was significantly lower than in those without sorafenib. Transcriptome analysis of zebrafish hearts revealed that expression of stanniocalcin1 (stc1) in zebrafish treated with sorafenib was significantly lower than that without sorafenib treatment. We were able to demonstrate that the ventricular dimension of the longitudinal axis in stc1 morphant was significantly smaller than that of control zebrafish and that forced expression of stc1 normalized the decrease in ventricular diameter in stc1 morphant and zebrafish treated with sorafenib. These data suggest that stc1 is the gene responsible for sorafenib-induced cardiotoxicity. Gene expression regulated by sorafenib in zebrafish at 4 dpf was measured. Four independent experiments were performed for each group.
2014-12-04 | E-GEOD-61155 | biostudies-arrayexpress
Project description:To further development of the gene expression, we have employed whole genome microarray expression profiling as a discovery platform to identify genes that are regulated in miR-132 knockdown zebrafish. Zebrafish larvae were injected with Control MO or miR-132 MO at one-cell stage. Then the upregulated genes are combined to the miRNA prediction alagorithm. 21 genes were picked up and verifed by luciferase assay. The total RNA was extracted from 3 dpf zebrafish injected with 8 ng control or miR-132 MO MO. The RNA was applied for the microarray gene proliling
2016-08-09 | E-GEOD-85291 | biostudies-arrayexpress
Project description:Fish, JE, Santoro, MM, Morton, SU, Yu, S, Yeh, RF, Wythe, JD, Ivey, KI, Bruneau, BG, Stainier, DYR, and Srivastava, D. (2008). miR-126 Regulates Angiogenic Signaling and Vascular Integrity. Developmental Cell 15, 272-284. Precise regulation of the formation, maintenance, and remodeling of the vasculature is required for normal development, tissue response to injury, and tumor progression. How specific microRNAs intersect with and modulate angiogenic signaling cascades is unknown. Here, we identified microRNAs that were enriched in endothelial cells derived from mouse embryonic stem (ES) cells and in developing mouse embryos. We found that miR-126 regulated the response of endothelial cells to VEGF. Additionally, knockdown of miR-126 in zebrafish resulted in loss of vascular integrity and hemorrhage during embryonic development. miR-126 functioned in part by directly repressing negative regulators of the VEGF pathway, including the Sprouty-related protein SPRED1 and phosphoinositol-3 kinase regulatory subunit 2 (PIK3R2/p85-β). Increased expression of Spred1 or inhibition of VEGF signaling in zebrafish resulted in defects similar to miR-126 knockdown. These findings illustrate that a single miRNA can regulate vascular integrity and angiogenesis, providing a new target for modulating vascular formation and function. Experiment Overall Design: To identify the genes regulated by miR-126 in vivo, flk1:GFP transgenic zebrafish embryos (which express GFP in the endothelium) were injected at the one-cell stage with 4 ng of two independent antisense morpholinos that block the processing of the miR-126 pri-cursor. At 48 hours post-fertilization, endothelial cells were isolated by fluorescence-activated cell sorting from flk1:GFP transgenic fish, and RNA was extracted. Arrays were performed on four biological replicates of control and two independent miR-126 morpholinos.
2008-10-25 | E-GEOD-12012 | biostudies-arrayexpress
Project description:The commercially available zebrafish (Danio rerio) gene expression microarray (4x44K format, Agilent G2519F-026437) was used to characterise the changes in gene expression levels in the ovary and brain of adult female zebrafish after exposure to 55, 553 and 5442 ng/L DRS for 14 days. Also, the transcriptional response in the brain of adult female zebrafish was characterised after exposure to mixtures of DRS and P4 at concentrations of 27+0.8, 277+8, 3119+123 (ng/L), respectively. This study was designed to achieve an understanding of the mode of action of DRS and steroid mixtures in zebrafish.
2014-06-04 | E-MTAB-2077 | biostudies-arrayexpress
Project description:To further characterize the roles of cortisol signaling via the glucocorticoid receptor (GR) in developing zebrafish, we have used morpholino oligonucleotides to knockdown GR protein translation and measured gene expression in RNA extracted from 24 and 36 hours post fertilization (hpf) embryos. The GR morpholino was characterized previously in Nesan et al., 2012, Endocrinology 181, 35-44) Single-cell zebrafish embryos were microinjected with either active morpholino or mispair control. Embryos were frozen at 24 and 36 hpf and total RNA extracted for microarray analysis. Three independent replicates (different breeding events on separate days) were performed for each treatment per timepoint.
2013-08-28 | E-GEOD-50376 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE12011: Regulation of human endothelial gene expression by miR-126 GSE12012: Regulation of zebrafish endothelial gene expression by miR-126 Refer to individual Series
2008-08-12 | E-GEOD-12039 | biostudies-arrayexpress