CB2 cannabinoid receptor agonist ameliorates Alzheimer-like phenotype in AβPP/PS1 mice

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• dc.contributor.author Aso Pérez, Esterca
• dc.contributor.author Juvés, Salvadorca
• dc.contributor.author Maldonado, Rafael, 1961-ca
• dc.contributor.author Ferrer, Isidreca
• dc.date.accessioned 2015-03-26T08:21:14Z
• dc.date.available 2015-03-26T08:21:14Z
• dc.date.issued 2013ca
• dc.description.abstract The specific CB2 cannabinoid receptor agonist JWH-133 induced cognitive improvement in double AβPP/PS1 transgenic mice, a genetic model of Alzheimer's disease. This effect was more pronounced when administered at the pre-symptomatic rather than the early symptomatic stage. The cognitive improvement was associated with decreased microglial reactivity and reduced expression of pro-inflammatory cytokines IL-1β, IL-6, TNFα, and IFNγ. In addition, JWH-133 reduced the expression of active p38 and SAPK/JNK, increased the expression of inactive GSK3β, and lowered tau hyperphosphorylation at Thr181 in the vicinity of amyloid-β plaques. Moreover, JWH-133 produced a decrease in the expression of hydroxynonenal adducts, and enhanced the expression of SOD1 and SOD2 around plaques. In contrast, the chronic treatment with JWH-133 failed to modify the amyloid-β production or deposition in cortex and hippocampus. In conclusion, the present study lends support to the idea that stimulation of CB2 receptors ameliorates several altered parameters in Alzheimer's disease such as impaired memory and learning, neuroinflammation, oxidative stress damage and oxidative stress responses, selected tau kinases, and tau hyperphosphorylation around plaques.
• dc.description.sponsorship This study was supported by grants from the Agrupació Mútua Foundation (XVII Award in the Elderly Field, to IF), Mutua Madrileña Foundation (IF), and BESAD-P project, CIBERNED, Instituto Carlos III (IF)
• dc.format.mimetype application/pdfca
• dc.identifier.citation Aso E, Juvés S, Maldonado R, Ferrer I. CB2 cannabinoid receptor agonist ameliorates Alzheimer-like phenotype in AβPP/PS1 mice. J Alzheimers Dis. 2013;35(4):847-58. DOI: 10.3233/JAD-130137ca
• dc.identifier.doi http://dx.doi.org/10.3233/JAD-130137
• dc.identifier.issn 1387-2877ca
• dc.identifier.uri http://hdl.handle.net/10230/23278
• dc.language.iso engca
• dc.publisher IOS Pressca
• dc.relation.ispartof Journal of Alzheimer's Disease. 2013;35(4):847-58
• dc.rights © IOS Press. All rights reservedca
• dc.rights.accessRights info:eu-repo/semantics/openAccessca
• dc.subject.other Alzheimer, Malaltia d'
• dc.subject.other Cannabinoides -- Ús terapèutic
• dc.title CB2 cannabinoid receptor agonist ameliorates Alzheimer-like phenotype in AβPP/PS1 miceca
• dc.type info:eu-repo/semantics/articleca
• dc.type.version info:eu-repo/semantics/acceptedVersionca