Investigating Increased Glutamate Transporter EAAT2 Function as a Potential Therapeutic Approach for Gulf War Illness
Abstract
Gulf War illness (GWI) is associated with a combination of exposure to war-related chemical agents and traumatic stress.Currently, there are no effective treatments, and the pathophysiology remains elusive. Neurological problems are among the most reported symptoms. In this study, we investigated the glutamatergic system in the hippocampi of mice exposed to war related chemical agents and stress. Mice developed GWI-like symptoms, including mood deficits, cognitive impairments, and fatigue. They exhibited the following pathological changes in hippocampi: elevated extracellular glutamate levels, impaired glutamatergic synapses, astrocyte atrophy, loss of interneurons, and decreased neurogenesis. LDN/OSU-215111 is a small molecule that can strengthen the structure and function of both the astrocytic processes and the glutamatergic synapses that together form the tripartite synapses. We found that LDN/OSU-215111 effectively prevented the development of mood and cognitive deficits in mice when treatment was implemented immediately following the exposure. When symptoms were already present, LDN/OSU-215111 still significantly ameliorated these deficits; impressively, benefits were sustained one month aftertreatment cessation. LDN/OSU-215111 effectively normalized hippocampal pathological changes. Overall, this study provides strong evidence that restoration of tripartite glutamatergic synapses by LDN/OSU-215111 is a potential therapy for GWI.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2020
- Accession Number
- AD1126312
Entities
People
- Chien-liang Lin
Organizations
- Ohio State University