Gulf War illness: Effects of repeated stress and pyridostigmine treatment on blood–brain barrier permeability and cholinesterase activity in rat brain

Amourette, Christine; Lamproglou, Ioannis; Barbier, Laure; Fauquette, William; Zoppe, Amélie; R, Viret; Diserbo, Michel

doi:10.1016/j.bbr.2009.05.002

Cited by 56 publications

(35 citation statements)

References 49 publications

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“…Consistent with reports that PB is unable to cross the blood-brain barrier (18), there were no significant effects of PB treatment on AChE activity in the head. However, AChE activity in the body was significantly inhibited in adult zebrafish treated with either 10 or 1000 µmol PB/L relative to controls ( Figure 4).…”

Section: Technical Objective 1: Establishment Of Gene Expression Profsupporting

confidence: 80%

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

Myers¹,

Williams²

2013

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR'S ACRONYM(S) U.S. Army Medical Research and Materiel CommandFort Detrick, Maryland 21702-5012 SPONSOR/MONITOR'S REPORT NUMBER(S) DISTRIBUTION / AVAILABILITY STATEMENTApproved for Public Release; Distribution Unlimited SUPPLEMENTARY NOTES ABSTRACTThe 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. SUBJECT TERMS EXECUTIVE SUMMARYSoldiers of the 1991 Gulf War were given the drug pyridostigmine bromide (PB) for pretreatment against nerve agents. This drug has since 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 for the characterization of the effects of pyridostigmine bromide on gene expression using unbiased, high-throughput techniques, specifically mRNA-seq. Additionally, we intended to study the PB response in the presence of factors that may modulate the effects of PB as indicated by epidemiological and experimental evidence, such as genetic variation or stress. Over the duration of the award, we have successfully characterized phenotypes associated with PB exposure and measured the molecular response using mRNA-seq. We further studied the effects of PB in the context of three different genetic backgrounds and under stressful conditions. Larval zebrafish were utilized to stu...

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Section: Technical Objective 1: Establishment Of Gene Expression Profsupporting

confidence: 80%

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

Myers¹,

Williams²

2013

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“…In fact the original insult is not needed to hold the system in this new regime, it will function in a stable fashion according to the new dynamics afforded by this alternate program. This concept is quite compatible with notions that male GWI is the result of past insults, whether from overexposure to acetylcholinesterase inhibitors (AChEI), 6,7 or exposure to depleted uranium, or petrol products. 75 We previously hypothesized that cholinergic modulation of endocrine-immune function during exercise differs in GWI subjects.…”

Section: Discussionmentioning

confidence: 56%

“…[2][3][4] Recent work in animal models has suggested in-theater exposure to acetylcholinesterase inhibitors as possible triggers of symptoms collectively referred to as Gulf War illness (GWI). These exposures include the stresspotentiated effects of DEET (N, N-Diethyl-meta-toluamide), 5 pyridostigmine bromide (PB), 6,7 and sarin. 8,9 Although the specific triggers continue to be investigated, studies involving molecular and cellular profiling in human subjects strongly support persistent immune dysfunction as a component of this complex disorder.…”

Section: Introductionmentioning

confidence: 99%

Succumbing to the laws of attraction

Fritsch

Craddock

Rosario

et al. 2013

Systems Biomedicine

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systems Biomedicine Volume 1 Issue 3 PF, TJAC, RMdR, and MAR performed computational simulations and analysis of computational results. PF, TJAC, ALS, VAF, and GB, compiled physiological data and developed the immune-endocrine connectivity network. PF, TJAC, and GB performed comparisons between experimental and computational data and interpreted the results. MAF and NGK collected and analyzed the experimental data. TJAC, RMdR, MAR, GdV, and GB conceived of the discrete logical analysis algorithm. All authors contributed to the drafting of this article, and approve of its contents.

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“…Additional surveys have been done using animal models and have focused on exposure to chemical agents used in theatre; namely organophosphates and acetylcholine esterase (AChE) inhibitors such as pyridostigmine bromide (PB) (Golomb, 2008;Amourette et al, 2009) and sarin (Shewale et al, 2012;Mach et al, 2008). Though much of this has focused on proteomic and phospho-proteomic profiling (Torres-Altoro et al, 2011;Zhu et al, 2010), recent work by Barbier et al (2009) surveyed the expression of genes associated with stress response, learning and memory in the hippocampus and hypothalamus of mice.…”

Section: Introductionmentioning

confidence: 99%

Altered immune pathway activity under exercise challenge in Gulf War Illness: An exploratory analysis

Broderick

Ben‐Hamo

Vashishtha

et al. 2013

Brain, Behavior, and Immunity

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Gulf War illness: Effects of repeated stress and pyridostigmine treatment on blood–brain barrier permeability and cholinesterase activity in rat brain

Cited by 56 publications

References 49 publications

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

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

Succumbing to the laws of attraction

Altered immune pathway activity under exercise challenge in Gulf War Illness: An exploratory analysis

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