Department of Psychiatry, Brain Research Center, The University of British Columbia, Vancouver, Canada.
Curr Alzheimer Res. 2010 May;7(3):255-61. doi: 10.2174/156720510791050948.
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 (Abeta); however it is unknown whether this effect is due to the cannabinoids' anti-inflammatory properties or whether it affects Abeta 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 Abeta 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.
大麻素已被证明可增加成年大脑中的神经发生，以及保护神经元免受兴奋毒性、钙离子内流、炎症和缺血的影响。最近的研究表明，合成大麻素可以减轻颅内淀粉样β蛋白（Abeta）处理的大鼠的水迷宫损伤；然而，尚不清楚这种作用是由于大麻素的抗炎特性，还是它影响 Abeta 的处理。在这里，我们研究了大麻素对体内阿尔茨海默病的影响。我们发现，强效合成大麻素 HU210 并未改善 APP23/PS45 双转基因 AD 小鼠模型的水迷宫性能或情境性恐惧条件反射任务。HU210 对 APP 处理和 Abeta 生成以及 AD 转基因小鼠大脑中的神经突斑块形成没有影响。我们的研究表明，合成大麻素 HU210 对 AD 模型小鼠的 AD 神经病理学和行为缺陷没有有益作用，这提醒人们在 AD 治疗中谨慎应用此类药物。
