dc.contributor.author |
Aso Pérez, Ester |
dc.contributor.author |
Palomer, Ernest |
dc.contributor.author |
Juvés, Salvador |
dc.contributor.author |
Maldonado, Rafael, 1961- |
dc.contributor.author |
Muñoz López, Francisco José, 1964- |
dc.contributor.author |
Ferrer, Isidre |
dc.date.accessioned |
2015-03-26T08:21:11Z |
dc.date.available |
2015-03-26T08:21:11Z |
dc.date.issued |
2012 |
dc.identifier.citation |
Aso E, Palomer E, Juvés S, Maldonado R, Muñoz FJ, Ferrer I. CB1 agonist ACEA protects neurons and reduces the cognitive impairment of AβPP/PS1 mice. J Alzheimers Dis. 2012;30(2):439-59. DOI: 10.3233/JAD-2012-111862 |
dc.identifier.issn |
1387-2877 |
dc.identifier.uri |
http://hdl.handle.net/10230/23277 |
dc.description.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. |
dc.description.sponsorship |
This study was supported by grants from the Spanish Ministry of Health (FIS PI08/0582 to IF; PI07/0593 to FJM), ERA-NET-NEURON (IF), Agrupació Mútua Foundation (XVII Award in the Elderly Field, to IF) and Mutua Madrileña Foundation (IF) |
dc.format.mimetype |
application/pdf |
dc.language.iso |
eng |
dc.publisher |
IOS Press |
dc.relation.ispartof |
Journal of Alzheimer's Disease. 2012;30(2):439-59 |
dc.rights |
© IOS Press. All rights reserved |
dc.subject.other |
Alzheimer, Malaltia d' |
dc.subject.other |
Farmacologia |
dc.subject.other |
Genètica |
dc.title |
CB1 agonist ACEA protects neurons and reduces the cognitive impairment of AβPP/PS1 mice |
dc.type |
info:eu-repo/semantics/article |
dc.identifier.doi |
http://dx.doi.org/10.3233/JAD-2012-111862 |
dc.rights.accessRights |
info:eu-repo/semantics/openAccess |
dc.type.version |
info:eu-repo/semantics/acceptedVersion |