Suppression of GWVI Toxin-Activated Microglia and Pathologies by DREADD
Abstract
Gulf War Illness (GWI) is characterized as a multisymptom disorder that is a major health burden to the Veteran community. Following their return from the war, Gulf War Veterans did not initially present with significant health issues, but these developed in high frequency in the years that follow. The delay between their deployment and the onset of chronic headaches, widespread pain, memory and concentration difficulties, persistent fatigue, respiratory problems, and affective psychological disorders has made it difficult for the medical community to accurately target a common underlying mechanism of the disorder. Recently, however, clinical research has detailed abnormal activity in immune systems of these Veterans. The immune system is uniquely dynamic because it is capable of retaining information about previous exposures to toxins or psychological traumas. Exposure to toxins specific to the Gulf War may have left permanent marks on their immune systems, increasing their susceptibility to develop symptoms observed in GWI. Because Veterans with the disorder often present with cognitive disabilities, immune cells specific to the brain, microglia, may be responsible for the long-term effects of the Gulf War. Our study is designed to address this possibility and to establish that by turning off microglia, using innovative chemogenetic techniques, we can prevent the onset of GWI-like symptoms that develop in a mouse model of the disorder, a model that recapitulates exposure to Gulf War toxins and psychological stress. New therapeutic approaches developed for other neurological indications selectively inhibit microglia. By establishing a critical role of microglia in the onset and progression of GWI, there could be significant evidence to test therapeutic approaches that inhibit microglia activity as a means to both prevent progression of the disorder and to improve the overall health of Veterans.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910513
Entities
People
- Giulio Maria Pasinetti
Organizations
- Icahn School of Medicine at Mount Sinai
- United States Army