Rossi F, Jankovski A, Sotelo C
Neuromorphologie, Développement, Evolution, INSERM Unité 106, Hôpital de la Salpétrière, Paris, France.
J Comp Neurol. 1995 Sep 4;359(4):663-77. doi: 10.1002/cne.903590412.
Regeneration of severed central axons is supposed to depend on two factors: a permissive local environment and the particular intrinsic properties of axotomized neurones. To assess the role of each of these factors in axonal regeneration, the capability of two particular axon populations of the adult mouse cerebellum to grow into target-specific (cerebellum) and target-unspecific (neocortex) embryonic grafts was determined. Purkinje cell and inferior olivary axons were transected by passing a microscalpel through the axial white matter of the cerebellar folia, particularly those of the anterior lobe. Immediately after the injury, solid transplants were placed in the lesion cavity. Purkinje cell axons were labelled by using anticalbindin immunocytochemistry, and olivocerebellar fibres were visualized by biotinylated dextran amine anterograde axonal tracing. Following axotomy, Purkinje cell axons appeared as thickened processes ending with large terminal clubs. Their morphology and number did not change up to the longest survival time considered (2 months), thereby confirming previous demonstrations that Purkinje cells survive axon injury (I. Dusart and C. Sotelo, 1994, J. Comp. Neurol. 347:211-232). Inferior olivary axons were thinner and bore smaller terminal bulbs. When embryonic cerebellar grafts, containing cortical and deep nuclear precursors, were placed close to the injured axons, olivocerebellar fibres vigorously regenerated into the transplants and ended in new climbing fibres along the dendrites of grafted Purkinje cells. By contrast, host Purkinje cell axons never showed any outgrowth towards the graft. Similarly, these axons failed to regenerate into grafts containing solely the rostromedial portion of the cerebellar anlage, mostly consisting of deep nuclear neurones, their main targets. Comparable results were obtained by transplanting embryonic neocortical tissue: inferior olivary axons also regenerated into the grafts, although with distinct terminal arbours without the climbing fibre phenotype, whereas Purkinje cell axons always failed to grow. These results provide the first direct demonstration that severed inferior olivary axons are able to regenerate. In addition, they show that the growth-permissive/-promoting conditions created by embryonic nervous tissue are not sufficient to induce the regeneration of every axonal type and allow us to hypothesise that successful regeneration depends on the interplay between environmental cues and intrinsic properties of the axotomized neurones.
人们认为，中枢轴突的再生取决于两个因素：一个是允许性的局部环境，另一个是轴突切断的神经元的特定内在特性。为了评估这些因素在轴突再生中的各自作用，确定了成年小鼠小脑的两个特定轴突群体向靶标特异性（小脑）和靶标非特异性（新皮层）胚胎移植物生长的能力。通过将微型手术刀穿过小脑叶片（特别是前叶的叶片）的轴向白质来横断浦肯野细胞和下橄榄核轴突。损伤后立即将实体移植物置于损伤腔内。使用抗钙结合蛋白免疫细胞化学标记浦肯野细胞轴突，通过生物素化葡聚糖胺顺行轴突追踪观察橄榄小脑纤维。轴突切断后，浦肯野细胞轴突表现为增粗的突起，末端为大的终末球。在最长观察存活时间（2个月）内，它们的形态和数量没有变化，从而证实了先前的研究结果，即浦肯野细胞在轴突损伤后能够存活（I. Dusart和C. Sotelo，1994年，《比较神经学杂志》347:211 - 232）。下橄榄核轴突较细，末端球较小。当含有皮质和深部核前体的胚胎小脑移植物靠近损伤的轴突放置时，橄榄小脑纤维会有力地再生到移植物中，并沿着移植的浦肯野细胞的树突终止于新的攀缘纤维。相比之下，宿主浦肯野细胞轴突从未向移植物显示出任何生长。同样，这些轴突也未能再生到仅包含小脑原基嘴内侧部分（主要由深部核神经元组成，是它们的主要靶标）的移植物中。通过移植胚胎新皮质组织也获得了类似的结果：下橄榄核轴突也再生到移植物中，尽管其终末分支不同，没有攀缘纤维表型，而浦肯野细胞轴突总是不能生长。这些结果首次直接证明了切断的下橄榄核轴突能够再生。此外，它们表明胚胎神经组织产生的生长允许/促进条件不足以诱导每种轴突类型的再生，并使我们能够假设成功的再生取决于环境线索与轴突切断的神经元的内在特性之间的相互作用。
