REGULATION OF SYNAPTOSOMAL 2-ARACHIDONOYLGLYCEROL HYDROLYSIS BY CANNABIS EXTRACTS DURING AGING

SALAS ROSICLER S.; PASCUAL A.C.; MILANO, P.G.; PASQUARÉ S.J.

Buenos Aires

Congreso; Reunión de Sociedades de Biociencias 2021-2021 LXVI Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2021

SAIC

Theavailability of the main neuroprotective endocannabinoid, 2-arachidonoylglycerol(2-AG),was found to decrease in rat cerebral cortex (CC) synaptosomes (syn)duringaging. It was also demonstrated that 2-AG metabolism can be modulated byits ownreceptors. Moreover, phytocannabinoids (PC) present in Cannabisextracts (CE),have been proposed as neuroprotective agents and are being usedin severalstudies to treat neurodegenerative processes. The aim of this studywas toevaluate if THC present in CE could modulate 2-AG hydrolysis bymonoacylglycerollipase (MAGL). To this end, delta-9-tetrahydrolcannabinol (THC)enriched CE wereobtained from Cannabis Y Griega female flowers, previouslygrinded and heated115°C for 40 min. Extractions were performed by adding 5%(w/v) ethanol,vortexed, sonicated and agitated. The mixture was centrifugedand thesupernatant was evaporated under stream of N2. THC,cannabidiol (CBD) andcannabinol (CBN) were quantified by HPLC. CC syn from adult (4-6 months) andaged (24-26months) rats were isolated by differential centrifugation andpurifiedin ficoll gradients. MAGL activity wasassessed by incubating syn witheither THC enriched CE (10-3-50 μM THC) or 1 μM pure THC, and [3H]-MAG,simultaneously. It was observed that CEcontaining 1 μM THC decreased MAGLactivity in aged (p=0.0166) but not in adultsyn (p>0.05). However, 1 μM pureTHC failed to modulate 2-AG hydrolysis(p>0.05). This findings, could suggestthat THC enriched CE could attenuatethe deregulation of 2-AG metabolismobserved in aging, and that this effectcould only be generated when syn areexposed to the PC in the presence of theentire CE.