Gulf war toxicant-induced effects on the hippocampal dendritic arbor are reversed by treatment with a Withania somnifera extract
Authors
Amaan Shaikh
Laboratory of Molecular Biology, Research & Development, Department of Veterans Affairs, VA New Jersey Health Care System, East Orange, NJ, United States
Kathleen Murray
Laboratory of Molecular Biology, Research & Development, Department of Veterans Affairs, VA New Jersey Health Care System, East Orange, NJ, United States
Vijayalakshmi Ravindranath
Centre for Brain Research, Indian Institute of Science, Bengaluru, India
Bruce Citron
Laboratory of Molecular Biology, Research & Development, Department of Veterans Affairs, VA New Jersey Health Care System, East Orange, NJ, United States
Gulf War Illness (GWI) is a multi-symptom disorder that manifests with fatigue, sleep disturbances, mood-cognition pathologies, and musculoskeletal symptoms. GWI affects at least 25% of the military personnel that served in Operations Desert Shield and Desert Storm from 1990 to 1991. We modeled Gulf War toxicant exposure in C57BL/6J mice by combined exposure to pyridostigmine bromide (an anti-sarin drug), chlorpyrifos (an organophosphate insecticide), and DEET (an insect repellent) for 10 days followed by oral treatment with Withania somnifera root extract for 21 days beginning at 12 weeks post-exposure. W. somnifera, commonly referred to as ashwagandha, has been used in traditional Ayurvedic medicine for centuries to improve memory and reduce inflammation, and its roots contain bioactive molecules which share functional groups with modern pain, cancer, and anti-inflammatory drugs. Previously, we observed that GWI mice displayed chronic reductions in dendritic arbor and loss of spines in granule cells of the dentate gyrus of the hippocampus at 14 weeks post-exposure. Here, we examined the effects of treatment with W. somnifera root extract on chronic dendrite and spine morphology in dentate granule cells of the mouse hippocampus following Gulf War toxicant exposure. GWI mice showed approximately 25% decreases in dendritic length (p < 0.0001) and overall dendritic spine density with significant reductions in thin and mushroom spines. GWI mice treated with the Ayurvedic W. somnifera extract exhibited dendritic lengths and spine densities near normal levels. These findings demonstrate the efficacy of the Ayurvedic treatment for neuroprotection following these toxic exposures. We hope that the extract and the neuronal processes influenced will open new avenues of research regarding treatment of Gulf War Illness and neurodegenerative disorders.
Keywords: Gulf War Illness, neurodegeneration, ayurveda, dendritic arborization, hippocampus, neuronal morphology, granule cells
Author Biographies
Amaan Shaikh, Laboratory of Molecular Biology, Research & Development, Department of Veterans Affairs, VA New Jersey Health Care System, East Orange, NJ, United States
School of Graduate Studies, Rutgers University, Newark, NJ, United States
Kathleen Murray, Laboratory of Molecular Biology, Research & Development, Department of Veterans Affairs, VA New Jersey Health Care System, East Orange, NJ, United States
School of Graduate Studies, Rutgers University, Newark, NJ, United States
Bruce Citron, Laboratory of Molecular Biology, Research & Development, Department of Veterans Affairs, VA New Jersey Health Care System, East Orange, NJ, United States
Department of Pharmacology, Physiology, & Neuroscience, Rutgers New Jersey Medical School, Newark, NJ, United States
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