School of Biomolecular and Biomedical Sciences, Conway Institute, University College Dublin, Dublin 4, Ireland.
Neurochem Res. 2019 Mar;44(3):703-713. doi: 10.1007/s11064-018-2513-z. Epub 2018 Mar 24.
Here we demonstrate for the first time that cannabidiol (CBD) acts to protect synaptic plasticity in an in vitro model of Alzheimer's disease (AD). The non-psycho active component of Cannabis sativa, CBD has previously been shown to protect against the neurotoxic effects of beta amyloid peptide (Aβ) in cell culture and cognitive behavioural models of neurodegeneration. Hippocampal long-term potentiation (LTP) is an activity dependent increase in synaptic efficacy often used to study cellular mechanisms related to memory. Here we show that acute application of soluble oligomeric beta amyloid peptide (Aβ) associated with AD, attenuates LTP in the CA region of hippocampal slices from C57Bl/6 mice. Application of CBD alone did not alter LTP, however pre-treatment of slices with CBD rescued the Aβ mediated deficit in LTP. We found that the neuroprotective effects of CBD were not reversed by WAY100635, ZM241385 or AM251, demonstrating a lack of involvement of 5HT, adenosine (A) or Cannabinoid type 1 (CB) receptors respectively. However in the presence of the PPARγ antagonist GW9662 the neuroprotective effect of CBD was prevented. Our data suggests that this major component of Cannabis sativa, which lacks psychoactivity may have therapeutic potential for the treatment of AD.
在这里，我们首次证明大麻二酚 (CBD) 可在阿尔茨海默病 (AD) 的体外模型中发挥保护突触可塑性的作用。大麻的非精神活性成分 CBD 先前已被证明可在细胞培养和神经退行性变的认知行为模型中抵抗β淀粉样肽 (Aβ) 的神经毒性作用。海马长时程增强 (LTP) 是一种与记忆相关的细胞机制的研究中常用的突触效能的活性依赖性增加。在这里，我们表明与 AD 相关的可溶性寡聚体 Aβ 的急性应用会减弱来自 C57Bl/6 小鼠海马切片 CA 区的 LTP。单独应用 CBD 不会改变 LTP，但 CBD 预处理可挽救 Aβ 介导的 LTP 缺陷。我们发现，CBD 的神经保护作用不会被 WAY100635、ZM241385 或 AM251 逆转，这表明 5HT、腺苷 (A) 或大麻素 1 型 (CB) 受体均无参与。然而，在 PPARγ 拮抗剂 GW9662 的存在下，CBD 的神经保护作用被阻止。我们的数据表明，这种缺乏精神活性的大麻主要成分可能具有治疗 AD 的治疗潜力。
