Nothias F, Dusart I, Roudier F, Peschanski M
Unité de Recherches de Physiopharmacologie du Système Nerveux, INSERM U 161, Paris, France.
Neuroscience. 1989;33(3):605-16. doi: 10.1016/0306-4522(89)90412-0.
It has been demonstrated elsewhere that fetal thalamic tissue, when transplanted as a cell suspension into the excitotoxically neuron-depleted adult somatosensory thalamus, can grow, differentiate, and receive projections from host afferents. In the present study, we used the same paradigm to analyse the transplanted neurons during their morphogenesis, i.e. during the first month after transplantation. Using various anatomical criteria, at the light and electron microscope levels, we compared the development of transplanted neurons with the normal ontogeny of homologous neuronal populations. Confined solely to the mechanically lesioned area during implantation at seven days post-grafting, the transplant increased in size to occupy most of the previously neuron-depleted area by the third week after grafting. The final size of the transplant thus depended upon the size of the lesion. At seven days post-grafting, the neurons were small in size and the cellular density was high. At this immature stage few synaptic contacts were visible and the ultrastructure was characterized by large extracellular spaces. At 10 days post-grafting, the size of the neurons had increased and the cellular density had decreased. Both an extensive dendritic proliferation and a simultaneous active synaptogenesis could also be observed. All these events continued to evolve and during the third week the neuropil progressively acquired more mature ultrastructural characteristics. Synaptic contacts exhibiting characteristics comparable to those observed in the intact thalamus also became more numerous. At 20 days post-grafting, axonal myelination had started, the development of the graft apparently stopped and the various criteria had stabilized. Until that developmental stage, growth of grafted neurons compared to that of normal thalamic ones. At later stages, however, grafted neurons failed to grow larger and did not reach the size of the homologous population in the adult animal. It seems, therefore, that transplants of thalamic fetal neurons can be used as a tool with which to study thalamic neuronal development, within definable limits.
在其他地方已经证明,当将胎儿丘脑组织作为细胞悬液移植到经兴奋性毒素处理而神经元缺失的成体体感丘脑中时,它能够生长、分化并接收来自宿主传入神经的投射。在本研究中,我们采用相同的模式来分析移植神经元在形态发生过程中的情况,即在移植后的第一个月内。我们利用各种解剖学标准,在光学显微镜和电子显微镜水平上,将移植神经元的发育与同源神经元群体的正常个体发育进行了比较。在移植后七天植入时,移植组织仅局限于机械损伤区域,到移植后第三周,其大小增加,占据了先前神经元缺失区域的大部分。因此,移植组织的最终大小取决于损伤的大小。移植后七天,神经元体积小,细胞密度高。在这个未成熟阶段,可见的突触联系很少,超微结构的特征是细胞外间隙大。移植后十天,神经元体积增大,细胞密度降低。还可以观察到广泛的树突增殖和同时发生的活跃突触形成。所有这些事件都在持续发展,在第三周,神经毡逐渐获得更成熟的超微结构特征。表现出与完整丘脑中观察到的特征相似的突触联系也变得更加丰富。移植后二十天,轴突髓鞘化开始,移植组织的发育明显停止,各种标准趋于稳定。直到那个发育阶段,移植神经元的生长与正常丘脑神经元的生长情况相当。然而,在后期阶段,移植神经元未能长得更大,也未达到成年动物中同源群体的大小。因此,似乎胎儿丘脑神经元移植可以在可定义的范围内用作研究丘脑神经元发育的工具。