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Title: Toxicogenomic Characterization of Molecular Mechanisms Contributing to Chlorpyrifos Neurotoxicity in Adult Male Rats [smallRNA-seq]      
keywords:
Transcriptome or Gene expression
ID:
PRJNA301355
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. Overall design: Adult male Long Evans rats were repeatedly exposed to subclinical doses of chlorpyrifos or vehicle control (peanut oil) for 21 consecutive days (study days 1-21). Two CPF formulations (3 or 10 mg/kg b.w./day) or an equal volume of the vehicle were administered daily by subcutaneous injection, approximately 24 h apart. On the study day 21, animals were euthanized and hippocampus tissues were collected for biochemical and transcriptomic analyses. The global RNA profiles of all test animals were obtained using the Affymetrix GeneChip microarrays. The Illumina sequencing technologies were employed to analyzed comprehensive profiles of mRNAs and small RNAs from the rats exposed to 10 mg/kg/day CPF or the unexposed control rats.
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landingpage: http://www.ncbi.nlm.nih.gov/bioproject/PRJNA301355
authentication:
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authorization:
none
name:
Rattus norvegicus
ncbiID:
ncbitax:10116
abbreviation:
NCBI
homePage: http://www.ncbi.nlm.nih.gov
ID:
SCR:006472
name:
National Center for Biotechnology Information
homePage: http://www.ncbi.nlm.nih.gov/bioproject
ID:
SCR:004801
name:
NCBI BioProject