Novel Therapeutic Approaches for the Treatment of Depression and Cognitive Deficits in a Rodent Model of Gulf War Veterans Illness
Abstract
Approximately 1/3rd of the returning veterans from the 1991 Persian Gulf War exhibit chronic multi-symptom illnesses that includes neurologic morbidities such as depression, anxiety and cognitive impairments. Amongst a host of causative factors, exposure to low-levels of the nerve gas Sarin is strongly implicated for expression of Gulf War Illness (GWI). Nerve agents similar to pesticides are organophosphate (OP) compounds. Here, we used various exposures (repeated low-dose to single high-dose) to OP diisopropyl fluorophosphate (DFP) over a 1 to 10-day period to approximate levels of Sarin exposure during the First Gulf War. We then tested the rats at 3-months post DFP exposure to reflect the current status of GW veterans. Using a battery of rodent behavioral assays, we observed the presence of symptoms of chronic depression, anxiety, and memory problems as characterized by increased immobility in the Forced Swim Test, anhedonia in the Sucrose Preference Test, anxiety in the Elevated Plus Maze, and spatial and recognition memory impairments in the Object Location/ Recognition Test. These rats also demonstrated neuronal damage in hippocampus, piriform cortex, amygdala, and thalamus. This animal model will help decipher molecular mechanisms for the expression of GWI neurological symptoms and screen effective treatment of GWIs.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2015
- Accession Number
- ADA626155
Entities
People
- Laxmikant S. Deshpande
Organizations
- Virginia Commonwealth University