Toxicogenomic Characterization of Molecular Mechanisms Contributing to Chlorpyrifos Neurotoxicity in Adult Male Rats
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ABSTRACT:
PROVIDER: PRJNA301351 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR2927560.fastq.gz | Fastqsanger.gz | |||
| SRR2927570.fastq.gz | Fastqsanger.gz | |||
| SRR2927580.fastq.gz | Fastqsanger.gz | |||
| SRR2927590.fastq.gz | Fastqsanger.gz | |||
| SRR2927561.fastq.gz | Fastqsanger.gz |
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Project description:Chlorpyrifos (CPF) is an organophosphorus pesticide (OP), and one of the most widely used pesticides in the world. Metabolites of CPF and other OPs continue to be identified in the majority of human samples, even in countries such as the United States where OP use is declining (Arcury et al., 2010). The effects of repeated occupational and environmental exposures to OPs are poorly understood, although human and animal studies consistently identify neurotoxicity as the primary endpoint of concern. Thus, occupational exposures to sublethal doses of CPF are consistently associated with problems in cognitive abilities, such as learning and memory but the biological mechanism(s) underlying this association remain speculative. To identify potential mechanisms of CPF neurotoxicity, we employed a rat model that simulated documented CPF exposures in Egyptian agricultural workers. We quantified mRNA expression profiles in the CA1 region of the hippocampus of adult male Long Evans (LE) rats administered CPF at 3 or 10 mg/kg/d (s.c.) for 21 days. Despite significant inhibition of cholinesterase activity by the end of the 21 d exposure period, the CPF-exposed rats displayed minimal signs of cholinergic toxicity. Distinct hippocampal mRNA and miRNA signatures were associated with CPF exposure. Toxicogenomics-based evidence identified increased expression of neuropeptide genes in the hippocampi of CPF-exposed rats, which have been shown to activate receptor-mediated signaling pathways involved in cell survival. The analysis of small non-coding RNA profiles suggested the possibility that miR132/212-mediated homeostatic regulatory pathways may also be activated by repeated exposures to CPF. These findings identify potential molecular effects that may contribute to neurobehavioral deficits.
2016-12-30 | GSE74676 | GEO
Project description:Chlorpyrifos (CPF) is an organophosphorus pesticide (OP), and one of the most widely used pesticides in the world. Metabolites of CPF and other OPs continue to be identified in the majority of human samples, even in countries such as the United States where OP use is declining (Arcury et al., 2010). The effects of repeated occupational and environmental exposures to OPs are poorly understood, although human and animal studies consistently identify neurotoxicity as the primary endpoint of concern. Thus, occupational exposures to sublethal doses of CPF are consistently associated with problems in cognitive abilities, such as learning and memory but the biological mechanism(s) underlying this association remain speculative. To identify potential mechanisms of CPF neurotoxicity, we employed a rat model that simulated documented CPF exposures in Egyptian agricultural workers. We quantified mRNA expression profiles in the CA1 region of the hippocampus of adult male Long Evans (LE) rats administered CPF at 3 or 10 mg/kg/d (s.c.) for 21 days. Despite significant inhibition of cholinesterase activity by the end of the 21 d exposure period, the CPF-exposed rats displayed minimal signs of cholinergic toxicity. Distinct hippocampal mRNA and miRNA signatures were associated with CPF exposure. Toxicogenomics-based evidence identified increased expression of neuropeptide genes in the hippocampi of CPF-exposed rats, which have been shown to activate receptor-mediated signaling pathways involved in cell survival. The analysis of small non-coding RNA profiles suggested the possibility that miR132/212-mediated homeostatic regulatory pathways may also be activated by repeated exposures to CPF. These findings identify potential molecular effects that may contribute to neurobehavioral deficits.
2016-12-30 | GSE74727 | GEO
Project description:Chlorpyrifos (CPF) is an organophosphorus pesticide (OP), and one of the most widely used pesticides in the world. Metabolites of CPF and other OPs continue to be identified in the majority of human samples, even in countries such as the United States where OP use is declining (Arcury et al., 2010). The effects of repeated occupational and environmental exposures to OPs are poorly understood, although human and animal studies consistently identify neurotoxicity as the primary endpoint of concern. Thus, occupational exposures to sublethal doses of CPF are consistently associated with problems in cognitive abilities, such as learning and memory but the biological mechanism(s) underlying this association remain speculative. To identify potential mechanisms of CPF neurotoxicity, we employed a rat model that simulated documented CPF exposures in Egyptian agricultural workers. We quantified mRNA expression profiles in the CA1 region of the hippocampus of adult male Long Evans (LE) rats administered CPF at 3 or 10 mg/kg/d (s.c.) for 21 days. Despite significant inhibition of cholinesterase activity by the end of the 21 d exposure period, the CPF-exposed rats displayed minimal signs of cholinergic toxicity. Distinct hippocampal mRNA and miRNA signatures were associated with CPF exposure. Toxicogenomics-based evidence identified increased expression of neuropeptide genes in the hippocampi of CPF-exposed rats, which have been shown to activate receptor-mediated signaling pathways involved in cell survival. The analysis of small non-coding RNA profiles suggested the possibility that miR132/212-mediated homeostatic regulatory pathways may also be activated by repeated exposures to CPF. These findings identify potential molecular effects that may contribute to neurobehavioral deficits.
2016-12-30 | GSE74726 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2016-12-30 | GSE74728 | GEO
Project description:Given the widespread use of insecticides in the environment, it is important to perform studies evaluating their potential effects on humans. Organophosphate insecticides, such as chlorpyrifos, are being phased out; however, the use of pyrethroids in household pest control is increasing. While chlorpyrifos is relatively well studied, much less is known about the potential neurotoxicity of cyfluthrin and other pyrethroids. To gain insights into the neurotoxicity of cyfluthrin, we compared and evaluated the toxicity profiles of chlorpyrifos and cyfluthrin in primary human fetal astrocytes. We found that at the same concentrations, cyfluthrin exerts as great as, or greater toxic effects on the growth, survival, and proper functioning of human astrocytes. By using microarray gene expression profiling, we systematically identified and compared the potential molecular targets of chlorpyrifos and cyfluthrin, at a genome-wide scale. We found that chlorpyrifos and cyfluthrin affect a similar number of transcripts. These targets include molecular chaperones, signal transducers, transcriptional regulators, transporters, and those involved in behavior and development. Further computational and biochemical analyses show that cyfluthrin and chlorpyrifos upregulate certain targets of the interferon-gamma and insulin-signaling pathways and that they increase the protein levels of activated extracellular signal-regulated kinase 1/2, a key component of insulin signaling; interleukin 6, a key inflammatory mediator; and glial fibrillary acidic protein, a marker of inflammatory astrocyte activation. These results suggest that inflammatory activation of astrocytes might be an important mechanism underlying neurotoxicity of both chlorpyrifos and cyfluthrin.
2007-10-26 | E-GEOD-5023 | biostudies-arrayexpress
Project description:Given the widespread use of insecticides in the environment, it is important to perform studies evaluating their potential effects on humans. Organophosphate insecticides, such as chlorpyrifos, are being phased out; however, the use of pyrethroids in household pest control is increasing. While chlorpyrifos is relatively well studied, much less is known about the potential neurotoxicity of cyfluthrin and other pyrethroids. To gain insights into the neurotoxicity of cyfluthrin, we compared and evaluated the toxicity profiles of chlorpyrifos and cyfluthrin in primary human fetal astrocytes. We found that at the same concentrations, cyfluthrin exerts as great as, or greater toxic effects on the growth, survival, and proper functioning of human astrocytes. By using microarray gene expression profiling, we systematically identified and compared the potential molecular targets of chlorpyrifos and cyfluthrin, at a genome-wide scale. We found that chlorpyrifos and cyfluthrin targeted a similar number of transcripts. These targets include chaperones, signal transducers, transcriptional regulators, transporters, and those involved in behavior and development. Further computational and biochemical analyses suggest that cyfluthrin and chlorpyrifos up-regulated certain targets of the interferon-gamma and insulin signaling pathways, and that they increased the protein levels of activated ERK1/2, a key component of insulin signaling; IL-6, a key inflammatory mediator; and GFAP, a marker of inflammatory astrocyte activation. These results suggest that inflammatory activation of astrocytes might be an important mechanism underlying neurotoxicity of both chlorpyrifos and cyfluthrin. Keywords: treatment comparison
2006-07-27 | GSE5023 | GEO
Project description:Toxicogenomic Characterization of Molecular Mechanisms Contributing to Chlorpyrifos Neurotoxicity in Adult Male Rats [microarray]
| PRJNA301140 | ENA
Project description:Toxicogenomic Characterization of Molecular Mechanisms Contributing to Chlorpyrifos Neurotoxicity in Adult Male Rats [RNA-seq]
| PRJNA301356 | ENA
Project description:Toxicogenomic Characterization of Molecular Mechanisms Contributing to Chlorpyrifos Neurotoxicity in Adult Male Rats [smallRNA-seq]
| PRJNA301355 | ENA
Project description:Chlorpyrifos (CPF) is an organophosphorus (OP) insecticide that is still widely used despite statutory restrictions on home use. CPF is converted to chlorpyrifos oxon (CPO) by oxidative desulfuration in liver. Paraoxonase (PON1) polymorphisms affects the catalytic efficiency of the hydrolysis of OPs, including CPO. We used both wt (PON1+/+) and PON1 knockout (PON1-/-) mice and PON1-/- mice carrying transgenes encoding the human alloforms tgHuPON1Q192 and tgHuPON1R192 to gain insight into the mechanisms of neurotoxicity of CPO throughout postnatal development, and to ascertain the importance of the PON1Q192R polymorphism for protecting against developmental toxicity of CPO. Whole-genome microarrays were used to measure gene expression changes associated with chronic CPO exposure of developing (PND 4-21) PON1-/-, tgHuPON1Q192R transgenic and PON1+/+ mice. Expression profiles are derived from cerebella from wild-type C57/Bl6 and PON1-/- on a C57/Bl6 background and two transgenic strains (tgHuPON1Q192, tgHuPON1R192) expressing either human PON1Q192 or human PON1R192 on the PON1-/- C57/Bl6 background. The mice were subjected to chronic postnatal exposure to CPO (CPO). Transgenic, PON1-KO and WT neonatal mice either treated with control (DMSO), 0.35 mg*kg-1*day-1 CPO or 0.5 mg*kg-1*day-1 CPO daily from PND 4 to PND 21. Chlorpyrifos (CPF) is converted to chlorpyrifos oxon (CPO) by oxidative desulfuration in liver. 55 arrays, 12 experimental groups (strain + treatment), due to QC issues the replicates are as follows; PON1-KO-0.35 (5), PON1-KO-.O5 (3), PON1-KO-DMSO (4), PON1-Q129-0.35 (5), PON1-Q129-0.5 (5), PON1-Q129-DMSO (4), PON1-R129-0.35 (5), PON1-R129-0.5 (5), PON1-R129-DMSO (4), WT-0.35 (6), WT-0.5 (3), WT-DMSO (6)
2011-11-09 | E-GEOD-25250 | biostudies-arrayexpress