Aso Pérez, EsterPalomer, ErnestJuvés, SalvadorMaldonado, Rafael, 1961-Muñoz, Francisco J.Ferrer, Isidro (Ferrer Abizanda)2016-03-142016-03-1420121387-2877https://hdl.handle.net/2445/96453The present study shows that chronic administration of the Cannabinoid receptor type 1 (CB1) receptor agonist arachidonyl-2-chloroethylamide (ACEA) at pre-symptomatic or at early symptomatic stages, at a non-amnesic dose, reduces the cognitive impairment observed in double AβPP(swe)/PS1(1dE9) transgenic mice from 6 months of age onwards. ACEA has no effect on amyloid-β (Aβ) production, aggregation, or clearance. However, ACEA reduces the cytotoxic effect of Aβ42 oligomers in primary cultures of cortical neurons, and reverses Aβ-induced dephosphorylation of glycogen synthase kinase-3β (GSK3β) in vitro and in vivo. Reduced activity of GSK3β in ACEA-treated mice is further supported by the reduced amount of phospho-tau (Thr181) in neuritic processes around Aβ plaques. In addition, ACEA-treated mice show decreased astroglial response in the vicinity of Aβ plaques and decreased expression of the pro-inflammatory cytokine interferon-γ in astrocytes when compared with age-matched vehicle-treated transgenic mice. Our present results show a beneficial effect of ACEA at both the neuronal, mediated at least in part by GSK3β inhibition, and glial levels, resulting in a reduction of reactive astrocytes and lower expression of interferon-γ. As a consequence, targeting the CB1 receptor could offer a versatile approach for the treatment of Alzheimer's disease.21 p.application/pdfeng(c) Asó, Ester et al., 2012Malaltia d'AlzheimerCànnabisCognicióNeuronesAlzheimer's diseaseCannabisCognitionNeuronsinfo:eu-repo/semantics/article6318162016-03-14info:eu-repo/semantics/openAccess22451318