CB2 Cannabinoid Receptor Agonist Ameliorates Alzheimer-Like Phenotype in AβPP/PS1 Mice

被引:154
作者
Aso, Ester [1 ]
Juves, Salvador [1 ,2 ]
Maldonado, Rafael [3 ]
Ferrer, Isidro [1 ,2 ]
机构
[1] Univ Barcelona, IDIBELL Hosp Univ Bellvitge, Inst Neuropatol, Serv Anat Patol, Lhospitalet De Llobregat, Spain
[2] Ctr Invest Biomed Red Enfermedades Neurodegenerat, Inst Carlos III, CIBERNED, Madrid, Spain
[3] Univ Pompeu Fabra, Dept Ciencies Expt Salut, Lab Neurofarmacol, Barcelona, Spain
关键词
Alzheimer's disease; CB2 cannabinoid receptor; cognition; neuroinflammation; oxidative stress; tau kinases; TAU-PROTEIN HYPERPHOSPHORYLATION; IN-VITRO; DISEASE; BRAIN; CANNABIDIOL; ACTIVATION; EXPRESSION; STRESS; LOCALIZATION; SYSTEM;
D O I
10.3233/JAD-130137
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The specific CB2 cannabinoid receptor agonist JWH-133 induced cognitive improvement in double A beta PP/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-1 beta, IL-6, TNF alpha, and IFN gamma. In addition, JWH-133 reduced the expression of active p38 and SAPK/JNK, increased the expression of inactive GSK3 beta, and lowered tau hyperphosphorylation at Thr181 in the vicinity of amyloid-beta 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-beta 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.
引用
收藏
页码:847 / 858
页数:12
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