The effects of donor stage on the survival and function of embryonic striatal grafts in the adult rat brain .1. Morphological characteristics
The effects of donor stage on the survival and function of embryonic striatal grafts in the adult rat brain .1. Morphological characteristics
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DOI：
10.1016/s0306-4522(96)00656-2
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发表时间：
1997-08-01
期刊：
影响因子：
3.3
通讯作者：
Dunnett, SB
中科院分区：
文献类型：
--
作者：
Fricker, RA;Torres, EM;Dunnett, SB
供体胚胎的阶段对来自不同神经元细胞类型的移植物的存活的影响已经被很好地记录。事实上，该参数已被证明是非常重要的存活和功能的移植的各种组织的中枢神经系统。然而，在将胚胎纹状体组织移植到亨廷顿病动物模型中的移植物中，这个问题尚未得到解决。在这项研究中，大鼠接受了单侧鹅膏蕈氨酸损伤的背侧纹状体接受移植物从标准解剖胚胎纹状体原基取自供体的胚胎阶段E14，E16，E17或E19天。移植后3个月，每组处死6只大鼠，用于移植物存活和形态学分析。在移植后10至14个月期间处死各组中的剩余动物。使用一系列标记物检测移植物形态，包括：乙酰胆碱酯酶和甲酚紫，32，000 mol. wt多巴胺和环AMP调节的磷蛋白（DARPP-32）、酪氨酸羟化酶和纹状体富集的磷酸酶。所有来自不同供体阶段的移植物在两个时间点均存活良好，甲酚紫染色表明神经元细胞类型遍布移植物。观察到移植物具有特征性的“斑片状"外观，具有密集的AChE活性和DARPP-32免疫阳性区域，其中散布有表达较轻的区域。这些区域还与富含磷酸酶和酪氨酸羟化酶的表达一致地共定位，这表明它们构成了移植物的纹状体样区室（所谓的P区，包含成熟纹状体的细胞），并接收特定的传入输入来自宿主多巴胺能系统。在移植后的两个时间点比较各组时，移植物总体积没有显着差异。然而，当比较P区的体积时，来自最年轻供体阶段（E14和E16）的纹状体原基产生具有显著更高比例的纹状体样组织的移植物。因此，为了增加这些移植物中纹状体组织的比例，应使用来自年轻胚胎供体的组织。这对该模型在亨廷顿病临床试验中的应用具有重要意义。(C)1997年IBRO。出版社：Elsevier Science Ltd
The effects of the stage of donor embryos on the survival of grafts from different neuronal cell types have been well documented. Indeed, this parameter has been shown to be highly important in the survival and function of transplants of various tissues of the CNS. However this question has not been addressed in grafts of embryonic striatal tissue transplanted into animal models of Huntington's disease. In this study, rats which had received a unilateral ibotenic acid lesion in the dorsal striatum received grafts from a standard dissection of embryonic striatal primordium taken from donors of embryonic stage either E14, E16, E17 or E19 days. Three months after transplantation six rats from each group were killed for analysis of graft survival and morphology. The remaining animals in each group were killed between 10 and 14 months after grafting. Graft morphology was detected using a range of markers including: acetylcholinesterase and Cresyl Violet, the 32,000 mol. wt dopamine- and cyclic AMP-regulated phosphoprotein (DARPP-32), tyrosine hydroxylase and striatally-enriched phosphatase. All the grafts from different donor stages survived well at both time-points and Cresyl Violet staining indicated neuronal cell types spread throughout the grafts. The transplants were seen to have a characteristic ''patchy'' appearance with areas of dense AChE activity and DARPP-32 immunopositivity interspersed with areas of much lighter expression. These areas also co-localized consistently with striatally-enriched phosphatase and tyrosine hydroxylase expression, indicating that they comprised the striatal-like compartment of the graft (the so called P zones, containing cells of the mature striatum), and receiving specific afferent input from the host dopaminergic system.There was no significant difference in total graft volume, when comparing individual groups at both time-points from grafting. However, when comparing the volume of the P zones, the striatal primordium from the youngest donor stages (E14 and E16) produced grafts with a significantly higher proportion of striatal-like tissue. Therefore, in order to increase the proportion of striatal tissue within these grafts, tissue from younger embryonic donors should be used. This has important implications in the application of this model towards clinical trials in Huntington's disease. (C) 1997 IBRO. Published by Elsevier Science Ltd.