Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/96453
Title: CB1 agonist ACEA protects neurons and reduces the cognitive impairment of AβPP/PS1 mice
Author: Asó, Ester
Palomer, Ernest
Juvés, Salvador
Maldonado, Rafael, 1961-
Muñoz, Francisco J.
Ferrer, Isidro (Ferrer Abizanda)
Keywords: Malaltia d'Alzheimer
Cànnabis
Cognició
Neurones
Alzheimer's disease
Cannabis
Cognition
Neurons
Issue Date: 2012
Publisher: IOS Press
Abstract: The 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.
Note: Reproducció del document publicat a: http://dx.doi.org/10.3233/JAD-2012-111862
It is part of: Journal of Alzheimer's Disease, 2012, vol. 30, num. 2, p. 439-459
Related resource: http://dx.doi.org/10.3233/JAD-2012-111862
URI: http://hdl.handle.net/2445/96453
ISSN: 1387-2877
Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (Patologia i Terapèutica Experimental)

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