Developing Zebra Fish Models for Interrogating Mitochondrial Disease, Performance, and Stress
Abstract
Topic Area: Primary, Mitochondrial Disease; Secondary, Dystonia, Psychotropic Medication, Congenital Heart Disease, and Chronic Migraine and Post-Traumatic Headache Overview: A broad spectrum of diseases, including neurodegenerative diseases such as Parkinson?s and Alzheimer?s, are caused by defects in mitochondrial function. The mitochondrion is the ?powerhouse? of the cell and produces energy for the body. However, mitochondria can become dysfunctional for several reasons including genetic mutations, age, and exposure to environmental toxins, such as those in the battlefield. Currently, there are no effective animal models to study mitochondrial dysfunction, and these studies cannot be done easily in humans. The group will develop zebrafish models to study mitochondrial dysfunction. Taking advantage of genetic approaches, a protein, referred to as ?MitoTimer? will be used to investigate mitochondrial aging in the neural and cardiac systems. Mitochondrial stress will also be induced using a variety of approaches, similar to that which a cell encounters with aging, from mutations, or from exposure to toxins in the environment. The team will also test if therapeutics can reverse the mitochondrial damage and lessen the negative impacts of the dysfunction. Thus, this group will develop a new model system to investigate mitochondrial aging and understand how mitochondrial dysfunction contributes to mitochondrial diseases including mitochondrial myopathy and neuropathy, dystonia, and heat disease. In addition, this model will be useful for studies to investigate how psychotropic medication affects Soldiers and Veterans. Critical Problem: The critical problem is that such models to investigate mitochondrial dysfunction are not currently available. An alternative model is the mouse, but mitochondria cannot be visualized in the living organism because they are not transparent. Moreover, the mouse model is expensive, models take more time to generate, and subsequent tests with drugs and toxins are difficult. Innovation: This is an innovative proposal because such models have not been previously available for studying mitochondrial dysfunction in the neural system as well as the cardiac tissue. Zebrafish are transparent during development, and mitochondrial function and trafficking can be studied in real time in the living organism. Moreover, the zebrafish model is a vertebrate model and has a developed neural and cardiac system that is very similar to humans. Applicability and Impact: As this new model system is established, it will be available for broad collaborative studies. Because mitochondria are involved in a broad range of diseases, as outlined by the numerous Peer Reviewed Medical Research Program Topics that are applicable, these studies will have broad impact. Products that aid performance, recovery, or treatment can be tested in the zebrafish model and advance studies into higher organisms such as mouse.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Aug 07, 2017
- Source ID
- W81XWH1710333
Entities
People
- Carla M. Koehler
Organizations
- United States Army
- University of California, Los Angeles