Repeated Exposure to Neurotoxic Levels of Chlorpyriphos Alters Hippocampal Expression of Neurotrophins and Neuropeptides

Abstract

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 mechanism(s) 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 mg/kg/d (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 mg/kg/d groups, respectively. Differential gene expression in the CA1 region of the hippocampus was observed only in the 10 mg/kg/d dose group relative to controls.

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Document Details

Document Type
Technical Report
Publication Date
Jan 13, 2016
Accession Number
AD1009522

Entities

People

  • Danielle L. Ippolito
  • David A. Jackson
  • John A. Lewis
  • Jonathan D. Stallings
  • Naissan Hussainzada
  • Pamela J. Lein
  • Young S Lee

Organizations

  • U.S. Army Center for Environmental Health Research

Tags

Communities of Interest

  • Biomedical

DTIC Thesaurus Topics

  • Acetylcholinesterases
  • Alzheimer Disease
  • Body Weight
  • Brain
  • Cell Membrane
  • Cells
  • Cellular Structures
  • Chemistry
  • Dementia
  • Diseases And Disorders
  • Environmental Health
  • Epilepsy
  • Gene Expression
  • Laboratory Animals
  • Medical Personnel
  • Neurodegeneration
  • Neurons

Fields of Study

  • Biology

Readers

  • Neuroscience
  • Neurotoxicology
  • Toxicology/Environmental Toxicology