School of Medicine, Western Sydney University, Campbelltown, Australia.
Neuroscience Research Australia (NeuRA), Randwick, Australia.
J Alzheimers Dis. 2020;74(3):937-950. doi: 10.3233/JAD-191242.
Alzheimer's disease (AD) is characterized by progressive cognitive decline and pathologically by the accumulation of amyloid-β (Aβ) and tau hyperphosphorylation causing neurodegeneration and neuroinflammation. Current AD treatments do not stop or reverse the disease progression, highlighting the need for more effective therapeutics. The phytocannabinoid cannabidiol (CBD) has demonstrated antioxidant, anti-inflammatory, and neuroprotective properties. Furthermore, chronic CBD treatment (20 mg/kg) reverses social and object recognition memory deficits in the AβPPxPS1 transgenic mouse model with only limited effects on AD-relevant brain pathology. Importantly, studies have indicated that CBD works in a dose-dependent manner. Thus, this study determined the chronic effects of 50 mg/kg CBD in male AβPPxPS1 mice. 12-month-old mice were treated with 50 mg/kg CBD or vehicle via daily intraperitoneal injections for 3 weeks prior to behavioral testing. A variety of cognitive domains including object and social recognition, spatial and fear-associated memory were evaluated. Pathological brain analyses for AD-relevant markers were conducted using ELISA and western blot. Vehicle-treated male AβPPxPS1 mice demonstrated impaired social recognition memory and reversal spatial learning. These deficits were restored after CBD treatment. Chronic CBD tended to reduce insoluble Aβ40 levels in the hippocampus of AβPPxPS1 mice but had no effect on neuroinflammation, neurodegeneration, or PPARγ markers in the cortex. This study demonstrates that therapeutic-like effects of 50 mg/kg CBD on social recognition memory and spatial learning deficits in AβPPxPS1 mice are accompanied by moderate brain region-specific reductions in insoluble Aβ40 levels. The findings emphasize the clinical relevance of CBD treatment in AD; however, the underlying mechanisms involved require further investigation.
阿尔茨海默病（AD）的特征是进行性认知能力下降，病理性地表现为淀粉样β（Aβ）的积累和 tau 过度磷酸化，导致神经退行性变和神经炎症。目前的 AD 治疗方法不能阻止或逆转疾病进展，这凸显了需要更有效的治疗方法。植物大麻素大麻二酚（CBD）具有抗氧化、抗炎和神经保护作用。此外，慢性 CBD 治疗（20mg/kg）可逆转 AβPPxPS1 转基因小鼠模型中的社会和物体识别记忆缺陷，而对 AD 相关的脑病理学仅有有限的影响。重要的是，研究表明 CBD 以剂量依赖的方式发挥作用。因此，本研究确定了 50mg/kg CBD 对雄性 AβPPxPS1 小鼠的慢性影响。12 月龄的小鼠接受 50mg/kg CBD 或载体通过每日腹腔注射 3 周，然后进行行为测试。评估了包括物体和社会识别、空间和与恐惧相关的记忆在内的多种认知领域。使用 ELISA 和 Western blot 对与 AD 相关标志物的病理性脑分析。与载体处理的雄性 AβPPxPS1 小鼠相比，社交识别记忆和空间学习的缺陷得到了恢复。慢性 CBD 治疗有降低 AβPPxPS1 小鼠海马中不溶性 Aβ40 水平的趋势，但对皮质中的神经炎症、神经退行性变或 PPARγ标志物没有影响。这项研究表明，50mg/kg CBD 对 AβPPxPS1 小鼠社交识别记忆和空间学习缺陷的治疗作用伴随着大脑特定区域不溶性 Aβ40 水平的适度降低。研究结果强调了 CBD 治疗 AD 的临床相关性；然而，需要进一步研究所涉及的潜在机制。
