Social regulation of oxidative stress in the brain

PROJECT SUMMARY The social environment can have both positive and negative impacts on health. In many social animals, individuals are competing for high social status, which can result in distinct social stressors for individuals with both high and low social status. Social stress can cause oxidative stress in the brain, which is a key mechanism driving a variety of mental health and neurodegenerative diseases. The overall objective of this proposal is to characterize the impact of social status on oxidative stress and its regulation across the brain. While low social status can be a source of chronic stress, high social status is also stressful - especially in natural conditions where defending social dominance is challenging. We hypothesize that the impact of social status on brain oxidative stress arises from a dynamic interplay between social stress and the hypothalamic-pituitary-gonadal (HPG) axis. Activation of this neuroendocrine center leads to the release of androgens, which facilitates competitive behavior, but is also known to modulate oxidative stress. We will test our hypothesis using the highly social cichlid fish Astatotilapia burtoni, a well-established model system for neurogenomics and integrated animal behavior, due in part to the large synteny and shared homologies of the neuroendocrine system relative to mammals. Male A. burtoni exist as two reversible phenotypes: dominant and subordinate. Dominant males aggressively defend a territory, have large gonads due to an upregulated HPG axis, and mate with females, while subordinate males are nonterritorial and reproductively suppressed. Social status can be readily manipulated and tracked in replicate groups. The proposal has the following specific aims: (1) Test how social status and HPG axis activity impact oxidative stress patterns across the brain using various markers of oxidative damage and antioxidant defense. (2) Determine the molecular mechanisms by which social status and HPG axis activity influence brain oxidative stress. At the completion of these aims, we will provide insights into how social status and HPG axis activity impact brain health and oxidative balance at the organismal level. The proposal is innovative because it investigates the regulation of oxidative balance in the brain in both dominant and subordinate individuals in a novel model system with a distinctly stratified dominance hierarchy. The proposed work is significant because oxidative stress in the brain has been causally linked to a range of psychopathologies, including depression and age-related brain disease. Our results will provide useful information that will ultimately be important for improving public health. The proposed research will expose undergraduate students to hypothesis-driven research addressing biomedically relevant questions.