Wang Y, Tien L T, Lapchak P A, Hoffer B J
Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan, ROC.
Cell Tissue Res. 1996 Nov;286(2):225-33. doi: 10.1007/s004410050691.
Previous reports have indicated that grafting of fetal ventral mesencephalic tissue to the nigra region of animals unilaterally lesioned with 6-hydroxydopamine (6-OHDA), in conjunction with kainate injection between the nigra and striatum, restores nigrostriatal tyrosine hydroxylase immunoreactivity. Glial-cell-line-derived neurotrophic factor (GDNF), a potent trophic factor for dopaminergic neurons, has been found to be upregulated by kainate. We have investigated the bridging effect of GDNF injection on intra-nigral transplants. Adult Sprague-Dawley rats were anesthetized and unilaterally injected with 6-OHDA into the medial forebrain bundle. The completeness of lesions was tested by measuring methamphetamine-induced rotations. Some 1-2 months after 6-OHDA administration, fetal ventral mesencephalic tissues were grafted into the lesioned nigral area followed by injection of 100 microg GDNF, along a tract from the nigra to striatum. Animals receiving transplantation and GDNF injection showed a significant decrease in rotation 1-3 months after grafting. Immunocytochemical studies indicated that tyrosine-hydroxylase-positive neurons and fibers were present in the nigra and striatum, respectively, after grafting. No effects of similarly injected brain-derived neurotrophic factor were seen. These results indicate that fetal nigral transplantation and GDNF injection restore the nigrostriatal dopaminergic pathway in Parkinsonian animals and support the hypothesis of trophic activity of GDNF on midbrain dopaminergic neurons.
先前的报告表明，将胎儿腹侧中脑组织移植到单侧用6-羟基多巴胺（6-OHDA）损伤的动物黑质区域，并在黑质和纹状体之间注射海藻酸，可恢复黑质纹状体酪氨酸羟化酶免疫反应性。胶质细胞源性神经营养因子（GDNF）是一种对多巴胺能神经元有效的营养因子，已发现它会被海藻酸上调。我们研究了GDNF注射对黑质内移植的桥接作用。将成年Sprague-Dawley大鼠麻醉，单侧向内侧前脑束注射6-OHDA。通过测量甲基苯丙胺诱导的旋转来测试损伤的完整性。在给予6-OHDA后约1-2个月，将胎儿腹侧中脑组织移植到损伤的黑质区域，然后沿着从黑质到纹状体的路径注射100微克GDNF。接受移植和GDNF注射的动物在移植后1-3个月旋转明显减少。免疫细胞化学研究表明，移植后黑质和纹状体中分别存在酪氨酸羟化酶阳性神经元和纤维。未观察到类似注射脑源性神经营养因子的效果。这些结果表明，胎儿黑质移植和GDNF注射可恢复帕金森病动物的黑质纹状体多巴胺能通路，并支持GDNF对中脑多巴胺能神经元具有营养活性的假说。
