Cheng David, Low Jac Kee, Logge Warren, Garner Brett, Karl Tim
Neuroscience Research Australia, Barker St, Randwick, NSW, 2031, Australia.
Psychopharmacology (Berl). 2014 Aug;231(15):3009-17. doi: 10.1007/s00213-014-3478-5. Epub 2014 Mar 1.
Patients suffering from Alzheimer's disease (AD) exhibit a decline in cognitive abilities including an inability to recognise familiar faces. Hallmark pathological changes in AD include the aggregation of amyloid-β (Aβ), tau protein hyperphosphorylation as well as pronounced neurodegeneration, neuroinflammation, neurotoxicity and oxidative damage.
The non-psychoactive phytocannabinoid cannabidiol (CBD) exerts neuroprotective, anti-oxidant and anti-inflammatory effects and promotes neurogenesis. CBD also reverses Aβ-induced spatial memory deficits in rodents.
Thus we determined the therapeutic-like effects of chronic CBD treatment (20 mg/kg, daily intraperitoneal injections for 3 weeks) on the APPswe/PS1∆E9 (APPxPS1) transgenic mouse model for AD in a number of cognitive tests, including the social preference test, the novel object recognition task and the fear conditioning paradigm. We also analysed the impact of CBD on anxiety behaviours in the elevated plus maze.
Vehicle-treated APPxPS1 mice demonstrated impairments in social recognition and novel object recognition compared to wild type-like mice. Chronic CBD treatment reversed these cognitive deficits in APPxPS1 mice without affecting anxiety-related behaviours.
This is the first study to investigate the effect of chronic CBD treatment on cognition in an AD transgenic mouse model. Our findings suggest that CBD may have therapeutic potential for specific cognitive impairments associated with AD.
患有阿尔茨海默病(AD)的患者表现出认知能力下降,包括无法识别熟悉的面孔。AD的标志性病理变化包括淀粉样蛋白-β(Aβ)聚集、tau蛋白过度磷酸化以及明显的神经退行性变、神经炎症、神经毒性和氧化损伤。
非精神活性植物大麻素大麻二酚(CBD)具有神经保护、抗氧化和抗炎作用,并能促进神经发生。CBD还能逆转Aβ诱导的啮齿动物空间记忆缺陷。
因此,我们在多项认知测试中,包括社会偏好测试、新物体识别任务和恐惧条件范式,确定了慢性CBD治疗(20mg/kg,每日腹腔注射3周)对AD的APPswe/PS1∆E9(APPxPS1)转基因小鼠模型的类似治疗效果。我们还分析了CBD对高架十字迷宫中焦虑行为的影响。
与野生型样小鼠相比,载体处理的APPxPS1小鼠在社会识别和新物体识别方面表现出损伤。慢性CBD治疗逆转了APPxPS1小鼠的这些认知缺陷,而不影响与焦虑相关的行为。
这是第一项研究慢性CBD治疗对AD转基因小鼠模型认知影响的研究。我们的研究结果表明,CBD可能对与AD相关的特定认知障碍具有治疗潜力。