Regulation of synaptosomal 2-arachidonoylglycerol hydrolysis by Cannabis extracts during aging

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

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

The availability of the main neuroprotective endocannabinoid, 2-arachidonoylglycerol (2-AG), was found to decrease in rat cerebral cortex (CC) synaptosomes (syn) during aging. It was also demonstrated that 2-AG metabolism can be modulated by its own receptors. Moreover, phytocannabinoids (PC) present in Cannabis extracts (CE), have been proposed as neuroprotective agents and are being used in several studies to treat neurodegenerative processes. The aim of this study was to evaluate if THC present in CE could modulate 2-AG hydrolysis by monoacylglycerol lipase (MAGL). To this end, delta-9-tetrahydrolcannabinol (THC) enriched CE were obtained from Cannabis Y Griega female flowers, previously grinded and heated 115°C for 40 min. Extractions were performed by adding 5% (w/v) ethanol, vortexed, sonicated and agitated. The mixture was centrifuged and the supernatant was evaporated under stream of N2. THC, cannabidiol (CBD) and cannabinol (CBN) were quantified by HPLC. CC syn from adult (4-6 months) and aged (24-26 months) rats were isolated by differential centrifugation and purified in ficoll gradients. MAGL activity was assessed by incubating syn with either THC enriched CE (10-3-50 μM THC) or 1 μM pure THC, and [3H]-MAG, simultaneously. It was observed that CE containing 1 μM THC decreased MAGL activity in aged (p=0.0166) but not in adult syn (p>0.05). However, 1 μM pure THC failed to modulate 2-AG hydrolysis (p>0.05). This findings, could suggest that THC enriched CE could attenuate the deregulation of 2-AG metabolism observed in aging, and that this effect could only be generated when syn are exposed to the PC in the presence of the entire CE.