Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch, and Volkswagenstiftung Research Group, Department of Experimental Neurology, Charité University Medicine, Berlin, Germany.
Cell Commun Signal. 2010 Jun 17;8:12. doi: 10.1186/1478-811X-8-12.
Adult neurogenesis is a particular example of brain plasticity that is partially modulated by the endocannabinoid system. Whereas the impact of synthetic cannabinoids on the neuronal progenitor cells has been described, there has been lack of information about the action of plant-derived extracts on neurogenesis. Therefore we here focused on the effects of Delta9-tetrahydrocannabinol (THC) and Cannabidiol (CBD) fed to female C57Bl/6 and Nestin-GFP-reporter mice on proliferation and maturation of neuronal progenitor cells and spatial learning performance. In addition we used cannabinoid receptor 1 (CB1) deficient mice and treatment with CB1 antagonist AM251 in Nestin-GFP-reporter mice to investigate the role of the CB1 receptor in adult neurogenesis in detail.
THC and CBD differed in their effects on spatial learning and adult neurogenesis. CBD did not impair learning but increased adult neurogenesis, whereas THC reduced learning without affecting adult neurogenesis. We found the neurogenic effect of CBD to be dependent on the CB1 receptor, which is expressed over the whole dentate gyrus. Similarly, the neurogenic effect of environmental enrichment and voluntary wheel running depends on the presence of the CB1 receptor. We found that in the absence of CB1 receptors, cell proliferation was increased and neuronal differentiation reduced, which could be related to CB1 receptor mediated signaling in Doublecortin (DCX)-expressing intermediate progenitor cells.
CB1 affected the stages of adult neurogenesis that involve intermediate highly proliferative progenitor cells and the survival and maturation of new neurons. The pro-neurogenic effects of CBD might explain some of the positive therapeutic features of CBD-based compounds.
成人神经发生是大脑可塑性的一个特殊例子，部分受内源性大麻素系统的调节。虽然已经描述了合成大麻素对神经元祖细胞的影响，但关于植物衍生提取物对神经发生的作用的信息却很少。因此，我们在这里重点研究了给予雌性 C57Bl/6 和巢蛋白-GFP 报告小鼠的 Delta9-四氢大麻酚（THC）和大麻二酚（CBD）对神经元祖细胞增殖和成熟以及空间学习表现的影响。此外，我们使用了大麻素受体 1（CB1）缺陷小鼠和 CB1 拮抗剂 AM251 在巢蛋白-GFP 报告小鼠中的处理，以详细研究 CB1 受体在成年神经发生中的作用。
THC 和 CBD 在空间学习和成年神经发生方面的作用不同。CBD 不会损害学习，但会增加成年神经发生，而 THC 则会降低学习而不影响成年神经发生。我们发现 CBD 的神经发生作用依赖于 CB1 受体，该受体在整个齿状回上表达。同样，环境富集和自愿轮跑的神经发生作用也依赖于 CB1 受体的存在。我们发现，在缺乏 CB1 受体的情况下，细胞增殖增加，神经元分化减少，这可能与 CB1 受体介导的 Doublecortin（DCX）表达中间祖细胞中的信号有关。
CB1 影响涉及中间高度增殖祖细胞以及新神经元存活和成熟的成年神经发生阶段。CBD 的促神经发生作用可能解释了基于 CBD 的化合物的一些积极治疗特征。
