Pyridostigmine Bromide, the Enteric Nervous System, and Functional Gastrointestinal Disorders in Gulf War Illness
Abstract
Gulf War illness (GWI) is a chronic, multi-symptom disorder with no treatment. Exposure to anti-cholinergic drugs such as pyridostigmine bromide(PB) contributed to the development of GWI, but the mechanisms that connect the acute effects of PB with chronic dysfunction in multiple systems remain unclear. Gastrointestinal problems are frequent and debilitating chronic symptoms experienced by Gulf War veterans. The overall objective of this proposal is to understand how PB contributes to the development of functional gastrointestinal disorders in Gulf War illness. Given that the enteric nervous system (ENS) regulates gut functions, we hypothesize that that PB disrupts gut functions by creating persistent neuroinflammation within the ENS. The major activities in this reporting period include in vivo and in vitro studies to understand the acute effects of PB on the ENS, the neural control of gut functions, and the inflammatory response within the gut. Key outcomes from this reporting period include observations showing that exposure to PB creates acute and chronic changes to gut functions that include increased fecal pellet output, higher fecal fluid content, slower colonic transit, altered neuromuscular control, defective intestinal barrier function, and neurodegeneration in the ENS. Our results show that the acute exposure to PB significantly alters the anatomy and functions of the ENS. We propose that these changes contribute to the pathophysiology of GWI.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2021
- Accession Number
- AD1128317
Entities
People
- Brian D Gulbransen
- David Fried
- Siomara Hernandez-rivera
Organizations
- Michigan State University