A cellular approach to understanding and treating Gulf War Illness

Philip L. Yates, Ankita Patil, Xiaohuan Sun, Alessia Niceforo, Ramnik Gill, Patrick Michael Callahan, Wayne Beck, Emanuela Piermarini, Alvin V. Terry, Kimberly A. Sullivan, Peter W. Baas, Liang Qiang

Research output: Contribution to journalArticlepeer-review

Abstract

Gulf War Illness (GWI), a disorder suffered by approximately 200,000 veterans of the first Gulf War, was caused by exposure to low-level organophosphate pesticides and nerve agents in combination with battlefield stress. To elucidate the mechanistic basis of the brain-related symptoms of GWI, human-induced pluripotent stem cells (hiPSCs) derived from veterans with or without GWI were differentiated into forebrain glutamatergic neurons and then exposed to a Gulf War (GW) relevant toxicant regimen consisting of a sarin analog and cortisol, a human stress hormone. Elevated levels of total and phosphorylated tau, reduced microtubule acetylation, altered mitochondrial dynamics/transport, and decreased neuronal activity were observed in neurons exposed to the toxicant regimen. Some of the data are consistent with the possibility that some veterans may have been predisposed to acquire GWI. Wistar rats exposed to a similar toxicant regimen showed a mild learning and memory deficit, as well as cell loss and tau pathology selectively in the CA3 region of the hippocampus. These cellular responses offer a mechanistic explanation for the memory loss suffered by veterans with GWI and provide a cell-based model for screening drugs and developing personalized therapies for these veterans.

Original languageEnglish (US)
JournalCellular and Molecular Life Sciences
DOIs
StateAccepted/In press - 2021

Keywords

  • Gulf War Illness
  • Human-induced pluripotent stem cells
  • Memory
  • Microtubule
  • Mitochondria
  • Neuronal activity
  • Tau

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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