ROLE OF A CANNABIS EXTRACT IN 2-ARACHIDONOYLGLYCEROL METABOLISM REGULATION DURING PHYSIOLOGICAL AGING

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

Bahía Blanca

Congreso; Reunión Anual AAFE 2024; 2025

Asociación Argentina de Farmacología Experimental

The availability of the main neuroprotective endocannabinoid (EC), 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 present in Cannabis sp. extracts (CE), capable of binding to cannabinoid receptors, are being used in several studies to treat neurodegenerative processes. The aim of the present work was to evaluate if a CE could modulate 2-AG metabolism and thus attenuate its deficit in aging. To this end, delta-9-tetrahydrocannabinol (THC) enriched CE were obtained from descarboxilated female flowers with ethanol as extraction solvent. The THC-free fraction (CE F/THC) was isolated from the CE using thin-layer chromatography. CC syn from adult (4-6 months) and aged (24-26 months) rats were obtained by differential centrifugation and purified in ficoll gradients, and then used to test the synthesis (diacylglycerol lipase -DAGL- and lysophosphatidate phosphohydrolase -LPAase- and hydrolysis (monoacylglycerol lipase, MAGL) of 2-AG. The syn were coincubated with THC enriched CE (1 μM THC), CE F/THC or 1 μM pure THC, and the respective radiolabeled substrate, simultaneously. Results showed that, none of the treatments modified the 2-AG metabolism in adult syn (p≥0.05). However, in aged syn, CE F/ THC caused a decrease in the MAGL (8%) and DAGL (84%) activities (p