01AP16-6 - Down-regulation of clock genes expression in the suprachiasmatic nuclei (SCN) after short-term propofol anesthesia. 
 
Ben-Hamouda N.1, Poirel V.-J.2, Dispersyn G.3, Pévet P.2, Challet E.2, Pain L.4 

1Centre Hospitalier Universitaire Vaudois, Service of Adult Intensive Care Medicine and Burns, Lausanne, Switzerland, 
2Institute of Cellular and Integrative Neurosciences, CNRS (UPR3212), University of Strasbourg, Department of Neurobiology of Rhythms, Strasbourg, France, 
3Institut de Recherche Biomédicale des Armées (IRBA), Dept of Neurosciences, Brétigny-sur-Orge, France, 
4Hopitaux Universitaires de Strasbourg, Dept of Anaesthesiology, Strasbourg, France 

Background & Goal of the Study: General anesthesia induced by propofol triggers phase-advances of circadian rhythms controlled by the master clock (Suprachiasmatic nuclei, SCN) only at certain times of the day (late resting period and early active period).1 Moreover, anesthesia induced by propofol has been associated with a subsequent reduction of Per2 mRNA levels in the whole brain.2 The acute effects of propofol anesthesia per se on the SCN molecular clockwork remain unclear. Here we aim to study expression of the clock genes Per1 and Per2 in the SCN of rats exposed to constant darkness after a single-dose injection of propofol or vehicle when the SCN clock is shifted by propofol. 

Materials and methods:  Thirty 2-months old, Long-Evans rats were randomly divided into 2 groups receiving an intraperitoneal administration of single dose of either 120 mg/kg propofol 1% (n=15), or intralipide® 10% (n=15) in late day (projected circadian time (CT) 10, i.e., 10h after the expected time of lights on). Thereafter, rats were sacrificed in darkness 1h, 2h or 3h after the treatment (projected CT11, CT12 or CT13; n=5 per time and treatment). In 20-µm brain coronal sections at the SCN level, we analyzed expression of Per1 and Per2 mRNA by radioactive in situ hybridization and quantification with NIH-ImageJ. The experiment was performed in accordance with the principles of laboratory animal care and the french laws. Data were analyzed with 2-way ANOVA. 

Results and discussion:  Propofol anesthesia induced a decrease in Per1 expression in the SCN at CT11 and CT12 when compared to the vehicle group. For Per1 expression (n=27), we found time (p< 0.001) and treatment effects (p=0.048). For Per2 expression (n=26), we observed a treatment effect (p=0.002), but no time effect. Thus, the expression of Per2 in the SCN is decreased at CT11 and CT12 after propofol anesthesia. In the absence of light, hypothermia and concomitant surgery, such down-regulation of Per genes is only correlated to propofol injection. This may explain post-anesthesia symptoms reported by patients. 

Conclusion:  We show here for the first time that short-term propofol anesthesia leads to a transient down-regulation of Per1 and Per2 expression in the master SCN clock. 

References:  
1. Challet E, Gourmelen S, Pevet P, et al. Neuropsychopharmacology 2007;32:728-35. 
2. Yoshida Y, Nakazato K, Takemori K, et al. Brain Res Bull 2009;79:441-4.