Neuroscience Program, Michigan State University, East Lansing, MI 48824, USA.
J Neuroimmune Pharmacol. 2012 Sep;7(3):533-8. doi: 10.1007/s11481-012-9375-y. Epub 2012 May 27.
Motor dysfunctions of Parkinson Disease (PD) are due to the progressive loss of midbrain nigrostriatal dopamine (NSDA) neurons. Evidence suggests a role for cannabinoid receptors in the neurodegeneration of these neurons following neurotoxicant-induced injury. This work evaluates NSDA neurons in CB1/CB2 knockout (KO) mice and tests the hypothesis that CB1/CB2 KO mice are more susceptible to neurotoxicant exposure. NSDA neuronal indices were assessed using unbiased stereological cell counting, high pressure liquid chromatography coupled with electrochemical detection or mass spectrometry, and Western blot. Results reveal that CB1 and CB2 cannabinoid receptor signaling is not necessary for the maintenance of a normally functioning NSDA neuronal system. Mice lacking CB1 and CB2 receptors were found to be equally susceptible to the neurotoxicant 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP). These studies support the use of CB1/CB2 KO mice for investigating the cannabinoid receptor-mediated regulation of the NSDA neuronal system in models of PD.
帕金森病（PD）的运动功能障碍是由于中脑黑质纹状体多巴胺（NSDA）神经元的进行性丧失。有证据表明，大麻素受体在神经毒性物质诱导的损伤后这些神经元的神经退行性变中起作用。这项工作评估了 CB1/CB2 敲除（KO）小鼠中的 NSDA 神经元，并测试了 CB1/CB2 KO 小鼠对神经毒性物质暴露更敏感的假设。使用无偏立体细胞计数、高压液相色谱与电化学检测或质谱联用以及 Western blot 评估 NSDA 神经元指数。结果表明，大麻素受体 CB1 和 CB2 的信号传导对于维持正常功能的 NSDA 神经元系统不是必需的。缺乏 CB1 和 CB2 受体的小鼠被发现同样容易受到神经毒性物质 1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）的影响。这些研究支持使用 CB1/CB2 KO 小鼠来研究大麻素受体介导的 PD 模型中 NSDA 神经元系统的调节。
