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May 16, 2017; 88 (20) Medical Hypothesis

Reprogramming cells from Gulf War veterans into neurons to study Gulf War illness

Liang Qiang, Anand N. Rao, Gustavo Mostoslavsky, Marianne F. James, Nicole Comfort, Kimberly Sullivan, Peter W. Baas
First published May 15, 2017, DOI: https://doi.org/10.1212/WNL.0000000000003938
Liang Qiang
From the Department of Neurobiology and Anatomy (L.Q., A.N.R., P.W.B.), Drexel University, Philadelphia, PA; and Center for Regenerative Medicine (G.M., M.F.J.) and School of Public Health (N.C., K.S.), Boston University, Boston, MA.
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Anand N. Rao
From the Department of Neurobiology and Anatomy (L.Q., A.N.R., P.W.B.), Drexel University, Philadelphia, PA; and Center for Regenerative Medicine (G.M., M.F.J.) and School of Public Health (N.C., K.S.), Boston University, Boston, MA.
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Gustavo Mostoslavsky
From the Department of Neurobiology and Anatomy (L.Q., A.N.R., P.W.B.), Drexel University, Philadelphia, PA; and Center for Regenerative Medicine (G.M., M.F.J.) and School of Public Health (N.C., K.S.), Boston University, Boston, MA.
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Marianne F. James
From the Department of Neurobiology and Anatomy (L.Q., A.N.R., P.W.B.), Drexel University, Philadelphia, PA; and Center for Regenerative Medicine (G.M., M.F.J.) and School of Public Health (N.C., K.S.), Boston University, Boston, MA.
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Nicole Comfort
From the Department of Neurobiology and Anatomy (L.Q., A.N.R., P.W.B.), Drexel University, Philadelphia, PA; and Center for Regenerative Medicine (G.M., M.F.J.) and School of Public Health (N.C., K.S.), Boston University, Boston, MA.
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Kimberly Sullivan
From the Department of Neurobiology and Anatomy (L.Q., A.N.R., P.W.B.), Drexel University, Philadelphia, PA; and Center for Regenerative Medicine (G.M., M.F.J.) and School of Public Health (N.C., K.S.), Boston University, Boston, MA.
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Peter W. Baas
From the Department of Neurobiology and Anatomy (L.Q., A.N.R., P.W.B.), Drexel University, Philadelphia, PA; and Center for Regenerative Medicine (G.M., M.F.J.) and School of Public Health (N.C., K.S.), Boston University, Boston, MA.
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Citation
Reprogramming cells from Gulf War veterans into neurons to study Gulf War illness
Liang Qiang, Anand N. Rao, Gustavo Mostoslavsky, Marianne F. James, Nicole Comfort, Kimberly Sullivan, Peter W. Baas
Neurology May 2017, 88 (20) 1968-1975; DOI: 10.1212/WNL.0000000000003938

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Abstract

Gulf War illness (GWI), which afflicts at least 25% of veterans who served in the 1990–1991 war in the Persian Gulf, is thought to be caused by deployment exposures to various neurotoxicants, including pesticides, anti–nerve gas pills, and low-level nerve agents including sarin/cyclosarin. GWI is a multisymptom disorder characterized by fatigue, joint pain, cognitive problems, and gastrointestinal complaints. The most prominent symptoms of GWI (memory problems, poor attention/concentration, chronic headaches, mood alterations, and impaired sleep) suggest that the disease primarily affects the CNS. Development of urgently needed treatments depends on experimental models appropriate for testing mechanistic hypotheses and for screening therapeutic compounds. Rodent models have been useful thus far, but are limited by their inability to assess the contribution of genetic or epigenetic background to the disease, and because disease-vulnerable proteins and pathways may be different in humans relative to rodents. As of yet, no postmortem tissue from the veterans has become available for research. We are moving forward with a paradigm shift in the study of GWI, which utilizes contemporary stem cell technology to convert somatic cells from Gulf War veterans into pluripotent cell lines that can be differentiated into various cell types, including neurons, glia, muscle, or other relevant cell types. Such cell lines are immortal and will be a resource for GWI researchers to pursue mechanistic hypotheses and therapeutics.

GLOSSARY

DFP=
di-isopropyl fluorophosphates;
GW=
Gulf War;
GWI=
Gulf War illness;
GWIC=
Gulf War Illness Consortium;
hiN=
human induced neurons;
hiPSC=
human induced pluripotent stem cells;
OP=
organophosphate;
PB=
pyridostigmine bromide

Footnotes

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Received September 30, 2016.
  • Accepted in final form February 23, 2017.
  • © 2017 American Academy of Neurology
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  • Article
    • Abstract
    • GLOSSARY
    • WHAT DO WE KNOW ABOUT GWI FROM RODENT MODELS AND CLINICAL STUDIES?
    • HUMAN INDUCED NEURONS—BRIDGING THE GAP WITH A PARADIGM SHIFT
    • RECRUITMENT PROCESS AND INFORMED CONSENT
    • CONTROL SAMPLES
    • EXPERIMENTAL PARADIGM
    • A NOTE TO PHYSICIANS
    • AUTHOR CONTRIBUTIONS
    • STUDY FUNDING
    • DISCLOSURE
    • ACKNOWLEDGMENT
    • Footnotes
    • REFERENCES
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