Repeated Exposure to Neurotoxic Levels of Chlorpyriphos Alters Hippocampal Expression of Neurotrophins and Neuropeptides
U.S. Army Center for Environmental Health Research (USACEHR) Fort Detrick United States
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Chlorpyrifos CPF, an organophosphorus pesticide OP, is one of the most widely used pesticides in the world. Subchronic exposures to CPF that do not cause cholinergic crisis are associated with problems in cognitive function i.e., learning and memory deficits, but the biological mechanisms underlying this association remain speculative. To identify potential mechanisms of subchronic CPF neurotoxicity, adult male Long Evans LE rats were administered CPF at 3 or 10 mgkgd s.c. for 21 days. We quantified mRNA and non-coding RNA ncRNA expression profiles by RNA-seq, microarray analysis and small ncRNA sequencing technology in the CA1 region of the hippocampus. Hippocampal slice immunohistochemistry was used to determine CPF-induced changes in protein expression and localization patterns. Neither dose of CPF caused overt clinical signs of cholinergic toxicity, although after 21 days of exposure, cholinesterase activity was decreased to 58 or 13 of control levels in the hippocampus of rats in the 3 or 10 mgkgd groups, respectively. Differential gene expression in the CA1 region of the hippocampus was observed only in the 10 mgkgd dose group relative to controls.