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Oligodendrocyte involvement in Gulf War Illness.

Jillian Belgrad1, Dipankar J Dutta1,2, Samantha Bromley-Coolidge1

  • 1Section on Nervous System Development and Plasticity, The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, Maryland.

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|July 25, 2019
PubMed
Summary

Gulf War illness (GWI) may involve damage to oligodendrocytes, crucial cells for nerve function. Exposure to nerve agents like sarin disrupted oligodendrocyte development and survival, suggesting a new pathway for GWI.

Keywords:
Gulf War illnessacetylcholineactivity-dependent myelinationcholinergiccorticosteronemyelinorganophosphateplasticitywhite matter

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Area of Science:

  • Neuroscience
  • Toxicology
  • Cell Biology

Background:

  • Gulf War illness (GWI) is a chronic multi-symptom disorder affecting veterans, potentially linked to low-level nerve agent exposure.
  • Acetylcholine plays a role in both synaptic transmission and communication between neurons and oligodendrocytes.

Purpose of the Study:

  • To investigate if Gulf War agents disrupt oligodendrocyte development.
  • To examine the effects of diisopropyl fluorophosphate (DFP), a sarin surrogate, and corticosterone on oligodendrocytes.

Main Methods:

  • Experiments using diisopropyl fluorophosphate (DFP) in rat prefrontal cortex (PFC) and corpus callosum.
  • In vitro cell culture studies with DFP and corticosterone on oligodendrocytes.
  • Assessment of oligodendrocyte proliferation, maturation, and survival.

Main Results:

  • DFP decreased the number of mature and dividing oligodendrocytes in the rat PFC.
  • DFP reduced oligodendrocyte survival in cell culture via a non-cholinergic mechanism.
  • Corticosterone promoted oligodendrocyte maturation and offered protection against DFP's effects.

Conclusions:

  • Oligodendrocyte development and survival are negatively impacted by Gulf War agents.
  • Both direct and indirect mechanisms, including neuron-glia interactions, contribute to DFP's detrimental effects.
  • Oligodendrocytes are a significant factor in the pathophysiology of Gulf War illness.