Grant: Doctoral Research Award: Canada Graduate Scholarships

Physical inactivity is a global health crisis that is associated with many debilitating chronic diseases (e.g., diabetes, cancer) and a decreased lifespan. Despite extensive research on its benefits, little is known about the physiological mechanisms controlling the motivation for exercise. Estrogens are a class of sex hormones and are very important regulators of physiology and behaviour. They can be produced in the brain, and previous research suggests that brain estrogens are important for regulating physical activity. The main goal of this project is to determine whether brain estrogen levels affect the motivation to exercise in rats, which are an excellent model for many aspects of human health and behaviour. Even a miniscule amount of estrogen can produce profound effects in target tissues, but current methods are not sensitive enough to detect very low levels in the brain. Therefore, we will first develop a robust and accurate method to measure estrogens in discrete brain regions. We will then use this method to test the effectiveness of the drug DHED in delivering estrogen exclusively to the brain. After administering DHED to rats, we will measure estrogens in the brain and compare them to levels in peripheral tissues. Although many neurological and psychiatric diseases are linked to abnormal changes in estrogen levels, there is currently no way to administer estrogen therapies specifically to the brain without causing harmful off-target effects elsewhere. Finally, we will treat rats with DHED and use a behavioural task to determine whether their motivation to wheel run (i.e., exercise) differs from untreated rats. Many drugs used to treat prostate and breast cancers decrease sex hormone signaling, and exercise improves quality of life for these patients. This study could lead to interventions that promote physical activity, increasing quality of life for these cancer patients and others with low estrogens, such as post-menopausal women.