Neurobehavioral protection by single dose l-deprenyl against MPTP-induced parkinsonism in common marmosets
Neurobehavioral protection by single dose l-deprenyl against MPTP-induced parkinsonism in common marmosets
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DOI：
10.1007/s00213-007-0929-2
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发表时间：
2008-01-01
影响因子：
3.4
通讯作者：
Tanioka, Yoshikuni
中科院分区：
文献类型：
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作者：
Ando, Kiyoshi;Maeda, Jun;Tanioka, Yoshikuni
目的以1-甲基-4-苯基-1，2，3，6-四氢吡啶（1-methyl-4-phenyl-1，2，3，6-tetrahydropyridine，MPTP）为对照药物，建立评价药物对帕金森病（Parkinson's disease，PD）行为保护作用的临床前方法。每天连续三天。对这些绒猴，胃内（i.g.）DEP 3组在每次MPTP给药前2 h预处理10 mg/kg DEP，DEP 1组仅在MPTP给药第一天预处理。结果蒸馏水组MPTP治疗后3周内活动次数明显减少，功能障碍评分明显增加。DEP组在MPTP后数天内出现与DW组相似的一过性变化，随后恢复至MPTP前水平。在上述行为观察后进行的放射自显影的结果表明，与另外制备的无MPTP的绒猴（n=5）的纹状体相比，在DW组绒猴的纹状体观察到明显较低的[C-11] PE 2 I（多巴胺转运体的配体）结合。DEP组中的绑定几乎相同的MPTP-自由的绒猴brain.Conclusion目前的临床前方法使用连续记录的活动绒猴在其生活的笼子里和放射自显影使用多巴胺转运蛋白配体可能是敏感的检测药物的保护作用帕金森病。
Objective Establishment of preclinical method evaluating behavioral protective actions of drugs for Parkinson's disease was attempted using l-deprenyl (DEP) as a reference drug in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-treated common marmosets.Materials and methods Fifteen marmosets received MPTP at 2 mg/kg, subcutaneously (s.c.) per day for three consecutive days. To these marmosets, intragastric (i.g.) administration of DEP at 10 mg/kg was pretreated 2 h before each MPTP administration in DEP3 group and pretreated only in the first MPTP administration day in DEP1 group. As a control, distilled water (DW) was pretreated before each MPTP administration (n=5 for each of three groups).Results In DW group, decreased daily activity counts and increased dysfunction scores were persistently observed for 3 weeks after MPTP. In DEP groups, the similar changes of both levels to those in DW group were temporally observed after MPTP for several days and then the values recovered to the pre-MPTP levels. The results of autoradiography performed after above behavioral observations indicated that markedly lower bindings of [C-11]PE2I (ligand for dopamine transporters) were observed at the striatum of DW group marmoset as compared with the striatum of additionally prepared MPTP-free marmoset (n=5). The bindings in DEP groups were almost the same as in the MPTP-free marmoset brains.Conclusion The present preclinical methods using continuous recording of activity of marmosets in their living cages and autoradiography using dopamine transporter ligand might be sensitive for detecting protective actions of drugs for Parkinson's disease.