Aso Pérez, EsterSànchez, Àlex (Sànchez Pla)Vegas Lozano, EstebanMaldonado, Rafael, 1961-Ferrer, Isidro (Ferrer Abizanda)2019-09-202019-09-202015-01-011387-2877https://hdl.handle.net/2445/140650Several recent findings suggest that targeting the endogenous cannabinoid system can be considered as a potential therapeutic approach to treat Alzheimer's disease (AD). The present study supports this hypothesis demonstrating that delta-9-tetrahydrocannabinol (THC) or cannabidiol (CBD) botanical extracts, as well as the combination of both natural cannabinoids, which are the components of an already approved cannabis-based medicine, preserved memory in AβPP/PS1 transgenic mice when chronically administered during the early symptomatic stage. Moreover, THC + CBD reduced learning impairment in AβPP/PS1 mice. A significant decrease in soluble Aβ42 peptide levels and a change in plaques composition were also observed in THC + CBD-treated AβPP/PS1 mice, suggesting a cannabinoid-induced reduction in the harmful effect of the most toxic form of the Aβ peptide. Among the mechanisms related with these positive cognitive effects, the anti-inflammatory properties of cannabinoids may also play a relevant role. Here we observed reduced astrogliosis, microgliosis, and inflammatory-related molecules in treated AβPP/PS1 mice, which were more marked after treatment with THC + CBD than with either THC or CBD. Moreover, other cannabinoid-induced effects were uncovered by a genome-wide gene expression study. Thus, we have identified the redox protein thioredoxin 2 and the signaling protein Wnt16 as significant substrates for the THC + CBD-induced effects in our AD model. In summary, the present findings show that the combination of THC and CBD exhibits a better therapeutic profile than each cannabis component alone and support the consideration of a cannabis-based medicine as potential therapy against AD.15 p.application/pdfeng(c) Aso, Ester et al., 2015Malaltia d'AlzheimerPèptidsCervellEfectes secundaris dels medicamentsMarihuanaFarmacologiaPlaquetes sanguíniesMetabolismeAlzheimer's diseasePeptidesBrainDrug side effectsMarijuanaPharmacologyBlood plateletsMetabolisminfo:eu-repo/semantics/article6476902019-09-20info:eu-repo/semantics/openAccess25125475