Effect of Synthetic Cannabinoid HU210 on Memory Deficits and Neuropathology in Alzheimer's Disease Mouse Model
Effect of Synthetic Cannabinoid HU210 on Memory Deficits and Neuropathology in Alzheimer's Disease Mouse Model
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DOI：
10.2174/156720510791050948
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发表时间：
2010-05-01
影响因子：
2.1
通讯作者：
Song, W.
中科院分区：
文献类型：
--
作者：
Chen, B.;Bromley-Brits, K.;Song, W.
大麻素已被证明可以增加成人大脑中的神经发生，并保护神经元免受兴奋性毒性，钙内流，炎症和缺血的影响。最近的研究表明，合成大麻素可以减轻用颅内淀粉样β蛋白（A β）治疗的大鼠的水迷宫损伤;然而，尚不清楚这种效果是否是由于大麻素的抗炎特性或是否影响A β加工。在这里，我们调查大麻素是否对体内阿尔茨海默病有任何影响。我们发现，HU 210，一种有效的合成大麻素，并没有改善水迷宫的性能或上下文恐惧条件反射任务中的APP 23/PS45双转基因小鼠模型的AD。HU 210对APP加工和A β生成以及AD转基因小鼠脑中的神经炎斑块形成没有影响。我们的研究表明，合成大麻素HU 210对AD模型小鼠的神经病理学和行为缺陷没有有益的影响，这提示此类药物在AD治疗中的应用应谨慎。
Cannabinoids have been shown to increase neurogenesis in adult brain, as well as protect neurons from excitotoxicity, calcium influx, inflammation, and ischemia. Recent studies have shown that synthetic cannabinoids can alleviate water maze impairments in rats treated with intracranial amyloid beta protein (A beta); however it is unknown whether this effect is due to the cannabinoids' anti-inflammatory properties or whether it affects A beta processing. Here we investigate whether cannabinoids have any effect on Alzheimer's disease in vivo. We found that HU210, a potent synthetic cannabinoid, did not improve water maze performance or a contextual fear conditioning task in an APP23/PS45 double transgenic mouse model of AD. HU210 had no effect on APP processing and A beta generation, as well as neuritic plaque formation in the brains of AD transgenic mice. Our study showed that synthetic cannabinoid HU210 had no beneficial effects on AD neuropathology and behavioral deficits of AD model mice, which advises caution of such drug's application in AD therapies.