Grant: Operating Grant

Periodic cessation of breathing during sleep - or sleep-disordered breathing (SDB) occurs in moderate or severe form in 1 of every 15 adult subjects, and in a large proportion of babies born before term. So far, there is no easy treatment options for SDB, and a drug-based therapy for SDB would be a remarkable breakthrough. The occurrence of this disorder is much lower in adult women because they have high circulating levels of progesterone, a sex hormone which acts on the brain to stimulate breathing. How precisely progesterone exerts this effect remains unknown. Broadly speaking, progesterone exerts its biological functions through different sets of specific receptors, the nuclear progesterone receptor (nPR) lies inside the nucleus of the cells and mediate some effects of progesterone by altering genes expression, while the membrane progesterone receptor (mPR) is inserted into the cellular membrane and mediate other effects of progesterone through intracellular biochemical pathways. My team have shown that these progesterone receptors are present in brain areas that are involved in the control of respiration, and the main objective of this proposal is to question the relative contribution of nPR and mPR on respiratory control and SDB during sleep in mice. We are using several strategies based on genetic disruption of expression of nPR and/or mPR to asses their relative contribution to respiratory control during sleep. So far or results tend to indicate that nPR and mPR exerts distinctive, and powerful effects on respiratory control during sleep, and reduces the occurrence of SDB in mice. These effects appear to be age, and sex-dependent. On the long-term, we hope that newly developed drugs targeting these receptors might become an available option for the development of a drug-based strategy for SDB.