Applying Genomic and Genetic Tools to Understand and Mitigate Damage from Exposure to Toxins

Abstract

The use of pyridostigmine bromide (PB) in the Gulf War of 1991 has been associated with increased incidence and symptom severity of Gulf War Illness. The goal of our research program was to use zebrafish as a model organism to characterize the effects of PB using locomotive/behavioral phenotyping and unbiased, high-throughput techniques, specifically mRNA-seq. Fish treated with PB exhibited perturbed behavioral patterns as indicated by changes in place preference. Exposure to PB altered expression of genes related to the synapse, calcium binding and signaling, cytoskeleton, cell junctions, oxidation-reduction reactions, and regulation of transcription in both larval and adult zebrafish. We studied the impact of genetic background using three strains of zebrafish. We also investigated the effect of stress on the PB response in both larval and adult zebrafish. The study of adult zebrafish allowed for characterization of tissue-specific gene expression in the brain and skeletal muscle, both immediately following PB exposure and at 8 weeks thereafter. These findings provide new insight into the effects of PB at the molecular level, which may aid in the development of therapies for Gulf War Illness.

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Document Details

Document Type
Technical Report
Publication Date
Oct 01, 2013
Accession Number
ADA592988

Entities

People

  • Kelly T. Williams
  • Richard M. Myers

Organizations

  • HudsonAlpha Institute for Biotechnology

Tags

DTIC Thesaurus Topics

  • Cell Membrane
  • Cell Physiological Processes
  • Cells
  • Cellular Structures
  • Chemistry
  • Cytoskeleton
  • Enzyme Inhibitors
  • Gene Expression
  • Genetics
  • Intercellular Junctions
  • Medical Personnel
  • Metabolism
  • Persian Gulf Syndrome
  • Pyridostigmine Bromide
  • Skeletal Muscle
  • Synapses

Fields of Study

  • Biology

Readers

  • Gulf War Illness and Chronic Multisymptom Illness in Veterans.
  • Molecular Genetics
  • Neurotoxicology

Technology Areas

  • Biotechnology