Sigma-1 Receptor Agonists as a Novel Therapeutic for Brain Mitochondrial Dysfunction in Gulf War Syndrome
Abstract
During the 1990-1991 Gulf War, approximately 700,000 U.S. troops were deployed to Persian Gulf theaters. At least 25% of them developed a chronic multisymptom health disorder called Gulf War Syndrome or Illness (GWI). Common GWI symptoms include cognitive impairment, fatigue, persistent muscle pain, and diarrhea. Even 25 years after the war, the Veterans with GWI still suffer from these severe symptoms. These symptoms are believed to be caused by prolonged exposure to chemical toxicants such as pesticides and anti-nerve gas pills. Such exposure causes damages to the central nervous system and thus results in cognitive problems. While it is critical to find how toxicants cause these persistent symptoms, it is more urgent to develop effective treatments to relieve such symptoms and improve the life quality of these GWI Veterans. Accordingly, the focus of the current study is to test drugs that can effectively relieve cognitive difficulties in GWI Veterans. Brain is composed of special cells called neurons, which have branches to connect each other for transmitting electrical signals. Neurons in different brain regions are specialized in various functions such as learning, memory, and motor coordination. For example, hippocampus and motor cortex are responsible for learning and memory while cerebrum controls motor coordination. The energy needed for neurons to transmit signals is mainly generated by the powerhouse within the neuron called mitochondria. A malfunction of mitochondria leads to low energy production, reduced neuron interconnection, and even the death of neurons. Damaged mitochondria are often observed in neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases and are believed to be responsible for cognitive decline in patients with these diseases. Several recent studies have indicated that mitochondrial damage in neurons, which is prevalent among GWI Veterans, is caused by exposure to pesticides and anti-nerve gas pills. If the damage to mitochondria is the main cause of cognitive problems in GWI Veterans, restoring mitochondrial function should lead to effective treatments. The goal of our proposed research is to use drugs that boost expression of a special protein, sigma-1 receptor, to effectively improve mitochondrial function and thus reverse cognitive decline (learning, memory, and motor coordination) in GWI Veterans. To validate our new treatment method, it is critical to test how effective the selected drugs are in improving mitochondrial function and cognitive abilities. Due to cost and safety considerations, we will use mice to test the effectiveness of these drugs. The reason to use mice for testing is that physiology and anatomy of mice are similar to those of human beings. In fact, many studies indicated that mice exposed to pesticides and anti-nerve gas pills developed cognitive problems similar to those of GWI Veterans. Because the drugs to be used in this study have been used in clinical trials to treat neurodegenerative diseases, they can soon be used in clinical trials to treat GWI Veterans. The proposed work will involve experts from different disciplines and with complementary expertise. Dr. Kai Shen is an expert in protein science and cell biology and has conducted substantial preliminary work on the protein sigma-1 receptor in the context of neurodegenerative diseases. Dr. Meharvan Singh, an established neurobiologist from the University of North Texas Health Science Center, has more than 20 years of experience studying neurodegenerative diseases. Their collaboration will ensure achievement of the research goal.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1710550
Entities
People
- Kai Shen
Organizations
- Savannah State University
- United States Army