Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USA.
J Neuroimmune Pharmacol. 2012 Mar;7(1):279-88. doi: 10.1007/s11481-011-9269-4. Epub 2011 Mar 24.
Acute intoxication with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induces nigrostriatal neurodegeneration that reflects Parkinson's disease (PD) pathobiology. The model is commonly used for rodent studies of PD pathogenesis and diagnostics and for developmental therapeutics. However, tests of motor function in MPTP-intoxicated mice have yielded mixed results. This unmet need reflects, in part, lesion severity, animal variability, and the overall test sensitivity and specificity. In attempts to standardize rodent motor function and behavioral tests, mice were trained on the rotarod or habituated in an open field test chamber, and baseline performance measurements were collected prior to MPTP intoxication. One week following MPTP intoxication, motor function and behavior were assessed and baseline measurements applied to post-MPTP measurements with normalization to PBS controls. Rotarod and open field tests assessed in this manner demonstrated significant differences between MPTP- and saline-treated mice, while tests of neuromuscular strength and endurance did not. We conclude that the rotarod and open field tests provide reliable measures of motor function for MPTP-intoxicated mice.
1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)急性中毒可诱导黑质纹状体神经退行性变,反映帕金森病(PD)的病理生物学。该模型常用于啮齿动物 PD 发病机制和诊断学的研究,以及发育治疗学的研究。然而,MPTP 中毒小鼠的运动功能测试结果喜忧参半。这种未满足的需求部分反映了病变严重程度、动物变异性以及整体测试的敏感性和特异性。为了尝试标准化啮齿动物的运动功能和行为测试,将小鼠在转棒上进行训练或在开放场测试室中适应环境,并在 MPTP 中毒前收集基线性能测量值。在 MPTP 中毒后一周,评估运动功能和行为,并将基线测量值应用于 MPTP 后测量值,同时与 PBS 对照进行归一化。以这种方式评估的转棒和开放场测试显示出 MPTP 处理组和盐水处理组之间存在显著差异,而神经肌肉力量和耐力测试则没有。我们得出结论,转棒和开放场测试为 MPTP 中毒小鼠提供了可靠的运动功能测量方法。