The time course of loss of dopaminergic neurons and the gliotic reaction surrounding grafts of embryonic mesencephalon to the striatum
The time course of loss of dopaminergic neurons and the gliotic reaction surrounding grafts of embryonic mesencephalon to the striatum
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DOI：
10.1006/exnr.1996.0141
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发表时间：
1996-09-01
影响因子：
5.3
通讯作者：
Fawcett, JW
中科院分区：
文献类型：
--
作者：
Barker, RA;Dunnett, SB;Fawcett, JW
将胚胎腹侧中脑组织移植到6-羟基多巴胺损伤大鼠的纹状体中，可以存活，并与宿主大脑建立和接受连接。移植的多巴胺能神经元可以在宿主大脑中生长，从而减轻这种实验性帕金森病的许多行为缺陷。然而，当植入后几周检查时，移植的黑质仅含有约5%的多巴胺能神经元的预期补充。我们研究了移植神经元丢失的时间过程。我们发现大多数人在移植后的前7天内死亡。然而，我们之前已经表明，与移植物相同尺寸的三维培养物，由相同的细胞悬浮液制成，具有更好的多巴胺能神经元存活。因此，移植物周围的环境中一定存在对多巴胺能神经元有毒的特征。多巴胺能移植物功效的一个限制因素是神经元能够在宿主脑中生长神经突并形成连接的距离很小。我们发现，从多巴胺能神经元到宿主纹状体的神经突起的生长发生在两个阶段。神经突在移植后7天内达到其最大长度，随后是慢得多的分支和末端形成过程。由于轴突生长在成人大脑可能会受到抑制的一些因素与反应性胶质增生，我们有免疫染色的波形蛋白？腱生蛋白、使用CS56抗体的硫酸软骨素蛋白聚糖（CS-PG）、使用OX-42抗体的DSD-1蛋白聚糖和小胶质细胞。我们已经把这个染色和一个简单的刺伤周围的染色做了比较。波形蛋白染色最初见于移植物及其周围的星形胶质细胞，7周时染色仅限于移植物周围的星形胶质细胞环。腱生蛋白、DSD-1和CS-PG最初见于移植物内和周围。到7周时，它们已经从移植物中消失，但CS-PG和腱生蛋白在刺伤周围仍然存在少量。一般来说，这些分子的免疫染色持续时间较长的刺伤病变周围比周围的移植。移植物和刺伤周围也有强烈的局部小胶质细胞反应，7周时大部分消退。(C)出版社：Academic Press，Inc.
Grafts of embryonic ventral mesencephalic tissue placed in the striatum of 6-hydroxydopamine-lesioned rats survive, and make and receive connections to and from the host brain. The dopaminergic neurons of the graft can grow processes into the host brain, and thereby alleviate many of the behavioral deficits of this form of experimental Parkinson's disease. However, when examined some weeks after implantation, grafted substantia nigra only contains about 5% of the expected complement of dopaminergic neurons. We have examined the time course of loss of grafted neurons. We find that the majority die during the first 7 days after transplantation. However, we have shown previously that three-dimensional cultures with the same dimensions as a graft, made of identical cell suspensions, have much better dopaminergic neuronal survival. There must, therefore, be features in the environment surrounding a graft that are toxic to dopaminergic neurons. A limiting factor in the efficacy of dopaminergic grafts is the small distance over which the neurons are able to grow neurites and form connections in the host brain. We find that the growth of neurites from dopaminergic neurons into the host striatum occurs in two phases. Neurites reach their maximum length within 7 days of transplantation, and this is followed by a much slower process of branch and terminal formation. Since axon growth in the adult brain may be inhibited by a number of factors associated with reactive gliosis, we have immuno-stained various ages of graft for vimentin? tenascin, chondroitin sulfate proteoglycan (CS-PG) using the CS56 antibody, the DSD-1 proteoglycan, and microglia using the OX-42 antibody. We have compared this staining with that surrounding a simple stab wound. Vimentin staining was initially seen in the graft and in astrocytes immediately surrounding it. By 7 weeks staining was restricted to a ring of astrocytes surrounding the graft. Tenascin, DSD-1, and CS-PG were initially seen in and around the grafts. By 7 weeks they had disappeared from grafts, but CS-PG and tenascin persisted in small amounts around stab wounds. In general, immunostaining of these molecules persisted longer around a stab lesion than around a graft. There was also an intense local microglial reaction surrounding both grafts and stab wounds which had largely resolved by 7 weeks. (C) 1996 Academic Press, Inc.