Omega-3 Polyunsaturated Fatty Acid Status, Microglial Activation, Stress Resilience, and Cognitive Performance
Abstract
The research proposed here relates to "integrative medicine (a Fiscal Year 2015 Peer Reviewed Medical Research Program Topic area) approaches for enhancing resilience and for treating psychological health issues in military and civilian populations." It is widely reported across mammalian species that a deficiency in the dietary intake of omega-3 polyunsaturated fatty acids, which is abundant in fish oil, negatively impacts a healthy individual s ability to tolerate stress and cognitive performance. In addition, a wealth of psychopathology literature also indicates a deficiency in omega-3 polyunsaturated fatty acids in people who have psychiatric disorders, including major depressive and bipolar disorders, attention-deficit disorder, and schizophrenia. Preliminary studies also suggest that omega-3 polyunsaturated fatty acid supplementation profoundly reduces transition to psychosis in individuals who are at high risk for schizophrenia. Thus, defining potential neuronal mechanisms that link omega-3 polyunsaturated fatty acids levels to behavioral deficits in humans and laboratory animals has important implications for basic neuroscience, as well as for public health, given that the trend of the modern diet has shown a reduction in omega-3 polyunsaturated fatty acid intake. One potential mechanism that likely explains the beneficial effects of omega-3 polyunsaturated fatty acids on multiple organ systems, such as heart, bones, and skin disorders, may relate to its ability to modulate the body s natural defense (or innate immune) system. Exposure to infection, trauma, toxic chemicals, and rarely certain natural proteins in the body (autoimmune factors) can trigger the innate immune system. This leads to inflammation, the body s protective response to remove exposure to the offending agent, along with clearing of the damage and promotion of the healing. In the brain, microglia are the primary immune cells that are activated in response to a hostile threat and promote inflammation in the brain. Recent studies indicate that increased brain inflammation in response to psychological stress and physiological trauma is a contributor to depression, suicide, and traumatic brain injury. Here, we propose human and rodent experiments to evaluate whether the anti-inflammation/proresolution effects of omega-3 polyunsaturated fatty acids contribute to the benefits in stress resilience and cognitive performance. These experiments focus on the expression of dietary omega-3 polyunsaturated fatty acid deficiency in late adolescence/young adulthood -- a developmentally critical period during which an individual is vulnerable to psychiatric disorders. In Aim 1, we will use a recently validated positron emission tomography imaging methodology to measure brain inflammation in young healthy individuals with low and high levels of omega-3 polyunsaturated fatty acids. In a parallel study in Aim 2, we will use an immune cell staining methodology to study inflammation in rodents that are deficient and adequate in omega-3 polyunsaturated fatty acids. We hypothesize that greater brain inflammation in omega-3 polyunsaturated fatty acid deficient humans/rodents will predict impairments in stress resilience and cognitive performance (both of which will be measured with a comprehensive battery of tests and rating scales in Aims 1 and 2). Such a finding would suggest that inflammation in the brain of individuals with chronic omega-3 polyunsaturated fatty acid deficiency leads to behavioral impairments. Furthermore, the proposed animal studies will evaluate whether brain inflammation and behavioral impairments can be reversed in young adults (vs. adolescents) with a diet enriched in omega-3 polyunsaturated fatty acids. The short-term impact of this proposal is that it will provide information about the mechanisms by which omega-3 polyunsaturated fatty acids lead to beneficial effects on stress resilience and cognitive performance in healthy individ
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610658
Entities
People
- Bita Moghaddam
Organizations
- United States Army
- University of Pittsburgh