Project Summary:
Over 10% of Wisconsinites are below the poverty line, while the 2022 Milwaukee Health Department’s Community Health Assessment Report found that 22% of residents reported exposure to discrimination and racism. Poverty, discrimination, housing and food insecurity all increase risk for mental and physical illness. While individuals can develop resilience to the negative consequences of stressor exposure, those at greatest risk often have the lowest access to resilience-producing resources, including the opportunity for regular physical activity.
The purpose of the studies in this proposal is to determine mechanisms that mediate the effects of physical activity to produce stress resilience. The team's long-term goal is to discover alternative approaches to achieve stress-resilience, perhaps without the need for regular physical activity.
These studies will explore the overarching hypothesis that brain concentrations of specific bioactive lipids are elevated in response to physical activity and evoke separate, complementary signaling pathways that produce stress resilience. These studies are supported by human studies showing that circulating concentrations of these mediators are increased during physical activity and by preclinical findings that they activate signaling pathways that dampen negative consequences of inescapable stress.
Project collaborator Dr. Greenwood will provide brain tissue from his well-validated rat model of physical activity-induced stress resilience and the team will test the hypotheses that physical activity-induced stress resilience is mediated by activation of CB1 receptor signaling and PPAR activation, through enhanced synthesis of allopregnanolone.
In addition, the project team will develop and test novel CRISP/Cas9 gene editing tools that they will leverage for future NIH applications. Successful completion of these studies will inform understanding of the molecular mechanisms that underpin physical activity-induced stress resilience, knowledge that can be leveraged to reduce the impact of environmental stress on the most vulnerable Wisconsin residents.