Prolonged oral cannabinoid administration prevents neuroinflammation, lowers β-amyloid levels and improves cognitive performance in Tg APP 2576 mice.
Prolonged oral cannabinoid administration prevents neuroinflammation, lowers β-amyloid levels and improves cognitive performance in Tg APP 2576 mice.
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DOI：
10.1186/1742-2094-9-8
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发表时间：
2012-01-16
影响因子：
9.3
通讯作者：
de Ceballos ML
中科院分区：
文献类型：
--
作者：
Martín-Moreno AM;Brera B;Spuch C;Carro E;García-García L;Delgado M;Pozo MA;Innamorato NG;Cuadrado A;de Ceballos ML
阿尔茨海默病(AD)的大脑显示出持续的炎症状态，非类固醇抗炎药可以降低患这种神经系统疾病的风险。大麻素是具有治疗潜力的神经保护和抗炎药。用两种不同药理作用的大麻素(Win 55、212-2和JWH-133)长期口服转基因淀粉样前体蛋白(APP)小鼠4个月，观察其对炎症和认知参数的影响，以及正电子发射断层扫描(PET)对18F-脱氧葡萄糖(18FDG)摄取的影响。在11个月龄的TG APP小鼠中，新物体识别显著减少，4个月的JWH能够使这种认知障碍正常化，尽管WIN无效。野生型小鼠的认知能力不会因服用大麻素而改变。TGAPP小鼠海马区和皮质区18FDG摄取减少，口服JWH可拮抗这一作用。海马区GFAP免疫反应性和皮质蛋白表达不受基因或治疗的影响。相反，TG APP小鼠Iba1阳性小胶质细胞密度增加，经JWH慢性治疗后恢复正常。两种大麻素均能有效抑制AD模型大鼠COX-2蛋白水平和肿瘤坏死因子-α基因表达的升高。在小鼠模型中，两种大麻素都显著降低了皮质β-淀粉样蛋白(Aβ)水平的升高。值得注意的是，这两种大麻素在体外都能促进Aβ通过脉络丛细胞的转运。综上所述，我们已经表明长期服用大麻素显示出明显的有益效果，同时伴随着炎症减轻和增加Aβ清除。
Alzheimer's disease (AD) brain shows an ongoing inflammatory condition and non-steroidal anti-inflammatories diminish the risk of suffering the neurologic disease. Cannabinoids are neuroprotective and anti-inflammatory agents with therapeutic potential. We have studied the effects of prolonged oral administration of transgenic amyloid precursor protein (APP) mice with two pharmacologically different cannabinoids (WIN 55,212-2 and JWH-133, 0.2 mg/kg/day in the drinking water during 4 months) on inflammatory and cognitive parameters, and on 18F-fluoro-deoxyglucose (18FDG) uptake by positron emission tomography (PET). Novel object recognition was significantly reduced in 11 month old Tg APP mice and 4 month administration of JWH was able to normalize this cognitive deficit, although WIN was ineffective. Wild type mice cognitive performance was unaltered by cannabinoid administration. Tg APP mice showed decreased 18FDG uptake in hippocampus and cortical regions, which was counteracted by oral JWH treatment. Hippocampal GFAP immunoreactivity and cortical protein expression was unaffected by genotype or treatment. In contrast, the density of Iba1 positive microglia was increased in Tg APP mice, and normalized following JWH chronic treatment. Both cannabinoids were effective at reducing the enhancement of COX-2 protein levels and TNF-α mRNA expression found in the AD model. Increased cortical β-amyloid (Aβ) levels were significantly reduced in the mouse model by both cannabinoids. Noteworthy both cannabinoids enhanced Aβ transport across choroid plexus cells in vitro. In summary we have shown that chronically administered cannabinoid showed marked beneficial effects concomitant with inflammation reduction and increased Aβ clearance.
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影响因子：
2.1
作者：
Chen, B.;Bromley-Brits, K.;Song, W.
通讯作者：
Song, W.
影响因子：
6.1
作者：
Coma M;Serenó L;Da Rocha-Souto B;Scotton TC;España J;Sánchez MB;Rodríguez M;Agulló J;Guardia-Laguarta C;Garcia-Alloza M;Borrelli LA;Clarimón J;Lleó A;Bacskai BJ;Saura CA;Hyman BT;Gómez-Isla T
通讯作者：
Gómez-Isla T
影响因子：
6.2
作者：
Halleskog C;Mulder J;Dahlström J;Mackie K;Hortobágyi T;Tanila H;Kumar Puli L;Färber K;Harkany T;Schulte G
通讯作者：
Schulte G
影响因子：
2.5
作者：
Baek, Jean Ha;Zheng, Yiwen;Smith, Paul F.
通讯作者：
Smith, Paul F.
影响因子：
9.3
作者：
Colton CA;Mott RT;Sharpe H;Xu Q;Van Nostrand WE;Vitek MP
通讯作者：
Vitek MP