Grant: Project Grant

Sleep apnea (SA) affects ~25% of the Canadian population. Respiratory instability and prolonged apneas during sleep indicate that parts of the nervous system regulating breathing are dysfunctional in SA patients. This is clinically important because SA increases the risk of disease, including cardiovascular problems. SA is ~2 times more frequent in men than women, thus indicating that ovarian hormones "protect" against respiratory problems. However, this ratio changes as women age and it is estimated that SA affects nearly half of post-menopausal women. Since loss of ovarian function is a normal part of life, this project aims to explain why menopause results in respiratory problems and hypertension in some women but not others. Because experiencing stress during early life affects brain development and increases vulnerability to disease, we propose that the consequences of menopause on respiratory function are aggravated by neonatal stress. Thus, the impact of early life stress on the cardiorespiratory system becomes apparent with loss of ovarian function. We will address this fundamental issue in female rats exposed to stress during early life. This model reproduces abnormalities in respiratory function and hypertension; in females, SA-related symptoms become apparent following loss of ovarian function. Experiments will be performed in the intact, naturally sleeping rats. We will then delve into the underlying mechanisms by quantifying the consequences of loss of ovarian function on the sensory, central, and neuroendocrine components of the respiratory control system of rats raised under normal conditions or subjected to neonatal stress in the form of neonatal maternal separation. As the Canadian population is aging, understanding the basic principles explaining such divergences in the aging trajectory of women is becoming urgent. This proposal offers a novel and comprehensive approach to an important health issue that affects a growing proportion of Canadians.