摘要
Summary
The expression of proenkephalin (PENK), prodynorphin (PDYN) and c-fos genes was studied in the striatum of C57B1/6 mice treated with 1-methyl-4-phenyl-1,2,3,6,-tetrahydropyridine (MPTP), which are used as a rodent model of Parkinson's disease (PD). Two weeks after systemic administration of MPTP (2×40 mg/kg, s.c. 18h apart), the lesion of the substantia nigra (SN) could be visualised by loss of the nigral tyrosine hydroxylase (TH) mRNA hybridization signal and by a 91% decrease in striatal dopamine levels. The levels of PENK and PDYN mRNAs were not significantly changed in the striatum of the lesioned mice, as compared to non-treated controls. The induction of the immediate early gene c-fos by the dopamine D2 receptor antagonist haloperidol was not altered, while the selective D1 receptor agonist SKF 38393 failed to induce c-fos in the striatum of MPTP-treated mice.
These results are in contrast to the data concerning rats with the 6-hydroxydopamine (6-OHDA) lesion of the SN, which serve as another rodent model of PD. In the striata of 6-OHDA-lesioned rats, PENK gene is upregulated, PDYN gene is down-regulated and the induction of c-fos gene by D2 receptor antagonists is abolished, whereas selective D1 receptor agonists induce c-fos gene, which does not occur in non-lesioned rats.
We presume that the lack of influence of the MPTP lesion in mice on the striatal gene expression was mainly caused by insufficient dopamine depletion in the striatum, which could not be increased in this model. The importance of the changes observed in 6-OHDA-lesioned rats has been discussed in the context of the mouse and primate MPTP models of PD. KeywordsMPTPmouseParkinson's diseasestriatumgene expressionproenkephalinprodynorphinc-fos
摘要译文
概述在用1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）处理的C57B1 / 6小鼠的纹状体中研究了脑啡肽（PENK），泼尼松啡（PDYN）和c-fos基因的表达），其用作帕金森病（PD）的啮齿动物模型。在全身施用MPTP两周后（2×40mg / kg，间隔18小时）黑质（SN）的病变可以通过黑质酪氨酸羟化酶（TH）mRNA杂交信号的损失和纹状体多巴胺水平的91％25的减少而可视化与未处理的对照组相比，损伤小鼠的纹状体中PENK和PDYN mRNA的水平没有显着变化多巴胺D 2受体拮抗剂氟哌啶醇诱导的立即早期基因c-fos没有改变，而选择性D 1受体激动剂SKF 38393不能在MPTP处理的小鼠的纹状体中诱导c-fos这些结果与关于具有SN的6-羟基多巴胺（6-OHDA）损伤的大鼠的数据形成对比，所述大鼠用作PDα的另一啮齿动物模型。在6-OHDA损伤的大鼠的纹状体中，PENK基因被上调，PDYN基因被下调，并且D 2受体拮抗剂对c-fos基因的诱导被消除，而选择性D 1受体激动剂诱导c-fos基因，这在非损伤大鼠中不发生我们推测，MPTP病变对小鼠纹状体基因表达缺乏影响主要是由于纹状体中多巴胺缺乏不足，其在该模型中不能增加。在6-OHDA-损伤的大鼠中观察到的变化的重要性已经在PD the的小鼠和灵长类动物MPTP模型的背景下讨论关键词：TPMPmouse帕金森氏病
B. Ziolkowska [1] ;G. Horn [2] ;A. Kupsch [2] ;V. Höllt [3]. The expression of proenkephalin and prodynorphin genes and the induction of c-fos gene by dopaminergic drugs are not altered in the striatum of MPTP-treated mice[J]. Journal of Neural Transmission - Parkinson's Disease and Dementia Section, 1995,9(2-3): 151–164