Targeting Mitochondrial Sphingolipids to Improve Brain Function in Gulf War Illness
Abstract
This application directly addresses the mechanisms of chronic neurobehavioral deficits in Gulf War illness (GWI). GWI is a multi-symptom disorder affecting about 30% of Veterans of Operation Desert Storm/Desert Shield – the 1991 Gulf War. Twenty-five years have elapsed since the Gulf War conflict, but Veterans continue to suffer from GWI, and there are no effective treatments available. Recent studies in GWI Veterans and rodent models of GWI underscore defects in mitochondria, which are powerhouse of the cell, as important contributors to neuropathology in GWI. Sphingolipids, a subset of lipids, are natural effectors of multiple mitochondrial functions. Our pilot studies in a mouse GWI model and in brain cells suggest that chronic accumulation of toxic sphingolipids may undermine mitochondrial function, thus contributing to neurobehavioral deficits. The proposed studies will determine the role of toxic sphingolipids and mitochondria in the pathogenesis of GWI and have the potential to uncover novel targets for therapeutic intervention. Three Food and Drug Administration (FDA)-approved drugs will be tested to correct the toxic sphingolipids and boost mitochondrial production of energy. Therefore, the results obtained from our novel studies could be rapidly translated to the Veteran population and will accelerate the development of more effective therapeutic approaches to rectify long-term neurological deficits in Veterans with GWI.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810230
Entities
People
- Sergei Novgorodov
Organizations
- Medical University of South Carolina
- United States Army