Sotelo C, Alvarado-Mallart R M
Nature. 1987;327(6121):421-3. doi: 10.1038/327421a0.
It has often been proposed that one way of replacing degenerating neurons in the brain is to implant embryonic neurons of the same type. However, in the case of so-called 'point-to-point' systems, as opposed to the 'paracrine' systems which mainly involve local release of neurotransmitter, functional recovery requires a precise re-establishment of the missing circuitry. We recently showed that in one point-to-point system, the cerebellum of adult mice homozygous for the mutation Purkinje cell degeneration (pcd)2, missing Purkinje cells can be replaced by grafting cerebellar primordia from normal mouse embryos. Here, we present studies of the cellular mechanisms underlying this successful replacement. Grafted Purkinje cells leave the graft to migrate along stereotyped pathways to their final position in the deficient molecular layer, where they receive synaptic contacts from adult host neurons. Both the detailed timetable and the precise cellular interactions observed are remarkably similar to those occurring during normal development. Our results suggest that the deficient molecular layer exerts a selective neurotropic effect on neurons of the missing category, and that the embryonic neurons are able to respond to this signal during a period defined by their own internal clock. We also raise the possibility that embryonic Purkinje cells can induce in adult neural cells a new type of plasticity, that of recreating a permissive microenvironment for the integration of embryonic neurons.
人们经常提出，替换大脑中退化神经元的一种方法是植入相同类型的胚胎神经元。然而，对于所谓的“点对点”系统，与主要涉及神经递质局部释放的“旁分泌”系统不同，功能恢复需要精确重建缺失的神经回路。我们最近发现，在一个点对点系统中，成年小鼠因Purkinje细胞退化（pcd）突变而纯合，缺失的Purkinje细胞可以通过移植正常小鼠胚胎的小脑原基来替代。在此，我们展示了这种成功替代背后的细胞机制研究。移植的Purkinje细胞离开移植物，沿着定型的路径迁移到缺陷分子层中的最终位置，在那里它们接受成年宿主神经元的突触接触。观察到的详细时间表和精确的细胞相互作用与正常发育过程中发生的情况非常相似。我们的结果表明，缺陷分子层对缺失类型的神经元发挥选择性神经营养作用，并且胚胎神经元能够在由其自身内部时钟定义的时期内对该信号作出反应。我们还提出了一种可能性，即胚胎Purkinje细胞可以在成年神经细胞中诱导一种新型的可塑性，即重新创建一个允许胚胎神经元整合的微环境的可塑性。
