THE CANNABINOID RECEPTOR CB1 IS EXPRESSED AND FUNCTIONAL IN ISOLATED NUCLEI OF RAT CEREBRAL CORTEX

GAVEGLIO, V.L.; PASCUAL, A.C.; GIUSTO, N.M.; PASQUARÉ, S.J.

Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

Lipids in nuclei are membrane components as well as signalingmolecules with a potential role in regulating gene transcription. Formerstudies from our lab demonstrated an active nuclear glycerolipidmetabolism in the central nervous system. We detected diacylglycerollipase, monoacylglycerol lipase, and lysophosphate phosphataseenzymatic activities, which are responsible for maintaining the levelsof endocannabinoid 2-arachidonoyl-glycerol (2-AG), a bioactivelipid mediator. The endocannabinoid system is a cellular signalingmechanism with a protective role in many pathophysiological processes,especially in the nervous system. 2-AG activates CB1 andCB2 GPCR receptors and triggers different signaling cascades,modulating intracellular Ca2+ levels, ERK1/2 phosphorylation, andother second messengers. Different studies have reported that CB1is expressed not only in plasma membrane but also in intracellularcompartments where they also seem to be functional. Therefore, theaim of this work was to study CB1 expression and function in isolatednuclei from rat cerebral cortex (CC). To this end, CC from Wistarrats were dissected, homogenized and highly purified nuclei (CCN)were isolated on a sucrose-density ultracentrifugation. CB1 proteinexpression was observed in CCN as well as in isolated cerebellumnuclei by Western Blot, which was confirmed by immunocytochemistry.In order to evaluate if CB1 is functional, CCN were incubated at37 °C with a CB1 agonist (WIN 55-212-2) and ERK1/2 and Akt signalingcascades were studied by Western Blot. Interestingly, it wasobserved that ERK1/2 phosphorylation increased in nuclei treatedwith WIN 5 μM for 30 min with respect to controls (p