Applying Genomic and Genetic Tools to Understand and Mitigate Damage from Exposure to Toxins
Final rept. 21 Sep 2009-20 Sep 2013
HUDSONALPHA INST FOR BIOTECHNOLOGY HUNTSVILLE AL
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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 locomotivebehavioral 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.
- Medicine and Medical Research