Environmental Disruption of Metabolism: Neurocognitive Consequences a Therapeutic Intervention
Abstract
Objectives and Rationale: Military service is associated with a high rate of mental health conditions, including post-traumatic stress disorder (PTSD). In addition, those who serve in the military have unavoidable exposures to toxic chemicals that are associated with various mental health conditions. How military-associated exposures increase the risk of PTSD and related disorders and whether this process can be reversed are not fully known. Based on our exciting preliminary data, this proposal will use mouse models to determine whether the common pollutants arsenic and hexavalent chromium increase the risk of PTSD by depleting the brain of essential fats required for normal neurological function. Furthermore, this work will go on to determine whether a unique approach to raising levels of these essential fats in the brain can reverse the effects of these toxic metals on neurological function. Such evidence will provide proof of principle for clinical trials in Service Members. Applicability and TERP Goals: This proposal addresses two TERP Program Goals. First, it will help us understand the ways in which exposure to two toxic metals promote the development of neurological disorders. Second, the proposed studies will directly address the goal of developing treatment approaches to minimize symptoms and disease progression resulting from such toxic exposures. Focusing on arsenic and hexavalent chromium, this work will address two overlapping Topic Areas, namely neurotoxins and other military service- related toxic metal exposures. Focus Areas covered by this proposal include unravelling the basic mechanisms of neurotoxicity and developing innovative treatments. Critically, these studies will establish protocols to study other service-associated toxic chemicals and the ability of lipid-based interventions to reduce their toxicity. Patients to Be Helped: The target population for these studies are U.S. personnel unable to avoid exposure to toxic metals because of the nature of their military service. In particular, those most likely to be helped by these studies are individuals exposed to toxic metals who are at high risk of service-associated mental health conditions such as PTSD. Clinical Applications, Benefits, and Risks: While this is an animal study, results from this study will lay the groundwork for improving the lives of patients in three important ways. First, it will help us better understand how exposure to toxic metals increases the risk of PTSD. Second, it will determine whether individuals exposed to toxic metals can be identified using non-invasive biomarkers. Finally, these studies will determine whether a novel fatty acid carrier molecule can restore levels of essential fats in the brain and alleviate the symptoms of PTSD after exposure has taken place. If confirmed, these studies will form the rationale for trials in humans. Projected Timeline: In the next 2 years, we will make important discoveries related to the ways in which toxic metals increase the risk of PTSD and other neurocognitive disorders. If confirmed, the following 3-5 years will be spent determining whether our intervention may work as a clinical therapeutic to improve the mental health of military Service Members and Veterans. At the same time, we will be exploring whether other toxic chemicals to which military members are exposed also operate by depleting the brain of essential fats and can thus be treated in similar ways. Contributions to Knowledge: This proposal will illuminate the ways in which toxic metals disrupt brain function. It will also determine whether biomarkers can be used to non-invasively determine whether someone has been exposed to toxic metals and is thus at risk for mental health disorders. Most importantly, we will determine whether a novel mechanism of restoring metabolic health to the brain can reverse the adverse effects of toxic metal exposures. Importantly, our framework to stu
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252311016
Entities
People
- Robert Sargis
Organizations
- United States Army
- University of Illinois at Chicago