帕金森病小鼠模型行为学检测方法的比较研究

Comparison of Behavioral Tests in MPTP-induced Parkinson's Disease in Mice

目的比较目前常用的5种帕金森病(PD)小鼠模型行为学检测方法在PD研究中的作用。方法用MPTP建立C57BL小鼠PD模型,通过行为学检测(自主活动计数、滚轴实验、游泳实验、爬杆实验、悬挂实验)、免疫组织化学和荧光分光光度法,对比5种行为学检测方法的平均数与变异系数,观察MPTP对PD小鼠模型的行为学、黑质多巴胺(DA)神经元和纹状体酪氨酸羟化酶免疫反应阳性(TH-ir)神经纤维以及纹状体DA水平的影响。结果给与MPTP后,小鼠行为学计数降低,爬杆实验未能得到检测结果,悬挂实验变异系数很高,结果有明显的偶然性,滚轴实验结果变异系数中等,平均数呈现一定的上升趋势,自主活动计数中移动与站立和游泳实验的平均数则呈现明显的下降趋势,变异系数很低,而黑质DA神经元数目减少约58%,纹状体TH-ir神经纤维密度减低,纹状体DA水平明显降低约88%,两组相比差异有显著性(P<0.01)。结论MPTP所致的C57BL小鼠的神经病理、生化改变与PD患者近似,自主活动计数和游泳实验优于其他行为学检测方法。

Objective To study the different role of 5 behavioral tests on 1-methyl-4-phenyl-1 ,2,3,6-tetrahydrepyridine （MPTP）-induced Parkinson＇s disease（PD） in C57BL mice. Methods The PD models were formed with intraperitoneal injections of MPTP. The effects of MPTP on behavioral exhibition, number of dopamine （DA） neurons in the substantia nigra and density of tyrosine hydroxylase-immunoreactive （TH-ir） nerve fibers in the striatum, level of DA in the striatum were studied by comparing 5 behavioral tests （open field, retarod, swim test, pole test, grid test）, immunohistochemical analysis and fluorespectrophotometry. Results The score of behavioral tests were declined after MPTP. But there was no efficient result in pole test. At the same time, there were high coefficient of variation （CV） and accidental result in grid test. The CV was intermediate and the result was moderately ascending in retared. In open field and swim test, the CV was low and the result was obviously downtrend. The number of DA neurons in the substantia nigra were decreased about 58%. The density of TH-ir nerve fibers was also showed to be reduced. The level of DA in the striatum were decresased about 88%. Conclusion The lesions induced by MPTP in C57BL mice are similar to PD in humans. Open field and swim tests are better than others in behavioral tests of studying MPTP-induced PD in C57BL mice.