Traitement des troubles mictionnels associés avec le syndrome métabolique avec modulateurs du système endocannabinoïde

 

Lysanne Campeau

Institut Lady Davis de recherches médicales de l'Hôpital général juif

 

Domaine : vieillissement

Programme chercheurs-boursiers cliniciens - Junior 1

Concours 2014-2015

Overactive bladder syndrome (OAB) is defined as voiding urgency usually with increased daytime and nighttime frequency. Medications that block certain receptors (muscarinics) can treat this condition, but only help the symptoms. One possible cause of OAB is the metabolic syndrome (MetS) that includes risk factors such as obesity, impaired sugar tolerance, high cholesterol, and high blood pressure. The cannabinoid system can potentially decrease the inflammation associated with MetS and OAB. Our goal is to determine if cannabinoid drugs can improve voiding problems associated with MetS by decreasing inflammation and oxidative stress.

First, we will describe the time course of the development of voiding problems in a rat model of MetS and compare to another established rat model, by associating it with biological inflammatory markers. We will provide a high cholesterol, high fructose diet in female rats and assess at different time points the voiding function with different tests. We will then assess changes in voiding function in rats after giving different doses of a cannabinoid receptor type 2 (CB2) agonist.

Second, we will characterize the voiding problems in a mouse model of MetS, using a similar diet as in rats, and compare it to an established mouse model. We will then apply it to mice that lack the CB2 receptor to understand its role in voiding problems.

Third, we will associate markers of inflammation and oxidative stress and plasma endocannabinoid levels with voiding function in women. Women with voiding symptoms will be recruited to receive a phase III licensed cannabinoid drug (Sativex) or a placebo for a period of four weeks.

The potential of cannabinoid drugs to decrease inflammation could help treat OAB associated with MetS. Overall, we will understand better the cause of OAB related to MetS in order to develop better drugs.