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: | Aso Pérez, 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 |
URI: | http://hdl.handle.net/2445/96453 |
Related resource: | http://dx.doi.org/10.3233/JAD-2012-111862 |
ISSN: | 1387-2877 |
Appears in Collections: | Articles publicats en revistes (Patologia i Terapèutica Experimental) Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
631816.pdf | 1.61 MB | Adobe PDF | View/Open |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.