Research Assistant Professor Texas A&M University Health Science Center College of Medicine
Rationale: Epilepsy is caused by genetic defects or acquired conditions such as brain injury, stroke or chemical neurotoxicity. Memory deficits and depression are main comorbidity in epilepsy and they affects the quality of life of patients more than the seizure frequency itself. However, the mechanisms underlying such devastating comorbidity remain unclear. One critical question is whether seizure neuropathology or seizure-independent pathways cause such comorbidity. Chronic non-epileptic conditions such as Gulf War Illness (GWI), a multi-symptom disease with striking cognitive and emotional impairments in veterans, may provide some molecular clues to epilepsy comorbidity. The aim of this study is to investigate the long-term neurological behavior in GWI-like (non-seizure) experimental model of chemical neurotoxicity in rats. Methods: GWI is linked to exposure to GWI-related chemicals during highly stressful Gulf war (pyridostigmine-bromide or PB and pesticides DEET, permethrin). Therefore, we induced an experimental GWI by four weeks of daily exposure to GWIR chemicals (PB, DEET, permethrin). Next, the control and GWI cohorts were screened for progressive changes in cognitive and emotional functions by using the novel object recognition memory test (NORT), open field test (OPT), elevated plus maze (EPM) test, and social interaction test (SIT). Results: At five-month post-GWI, rats exhibited statistically significant signs of memory dysfunction and emotional impairments. Exposure to GWI chemicals causes >70% decrease in time spent with the novel object in the NORT, >65% decrease in time spent in the central zone in the OFT, >55% decrease in time spent on open arms, and >80% decrease in open arm entries in the EPM, confirming strong deficits in memory and behavior. In addition, they displayed heightened aggressive score and significant decrease in social interactive time in the SIT, which indicates severe stressful anxiety and depression. Conclusions: These results confirm that chronic GWI chemical exposure led to cognitive and mental disorders, especially without obvious seizure activity, demonstrating the role of divergent etiological mechanisms in epilepsy and its comorbidity. Funding: Please list any funding that was received in support of this abstract.: DOD Award # W81XWH1910702 and NIH CounterACT Grants U01-NS083460 & R21 NS099009.