Caroni P
Friedrich Miescher Institute, Basel, Switzerland.
Essays Biochem. 1998;33:53-64. doi: 10.1042/bse0330053.
Specificity of connectivity is essential to nervous system function. It is determined by intrinsic programmes of gene expression that define neuronal phenotypes, and by activity-dependent mechanisms. Neuro-regeneration in the adult may involve re-activation of growth programmes within the constraints of neuron-type specific phenotypes. Lesion-induced re-induction of an axonal growth mode in adult neurons correlates with a vigorous cell body reaction that can also lead to apoptotic cell death. Directing the cell body reaction towards regeneration is a major goal towards improving regeneration. Extrinsic factors that prevent axonal regeneration in the adult CNS of higher vertebrates include inhibitory components on the surface of oligodendrocytes and CNS myelin, and proteoglycans associated with scar material; grafts of certain glial cells can promote regeneration. Local nerve sprouting and synaptic plasticity can produce dramatic functional adaptation to lesions in the adult and greatly enhance the impact of the partial regeneration of lesioned axons; nerve sprouting is promoted by diffusible and contact-mediated extrinsic mechanisms, and by intrinsic neuronal components. As a result of recent discoveries, significant progress in promoting axonal regeneration and recovery of function in the adult can be anticipated.
连接特异性对于神经系统功能至关重要。它由定义神经元表型的基因表达内在程序以及活动依赖机制所决定。成体中的神经再生可能涉及在神经元类型特异性表型的限制内重新激活生长程序。损伤诱导成体神经元轴突生长模式的重新诱导与强烈的细胞体反应相关,这种反应也可能导致凋亡性细胞死亡。引导细胞体反应走向再生是改善再生的一个主要目标。在高等脊椎动物的成体中枢神经系统中,阻止轴突再生的外在因素包括少突胶质细胞和中枢神经系统髓鞘表面的抑制成分,以及与瘢痕物质相关的蛋白聚糖;某些神经胶质细胞的移植可以促进再生。局部神经芽生和突触可塑性可以对成体中的损伤产生显著的功能适应,并极大地增强损伤轴突部分再生的影响;神经芽生由可扩散和接触介导的外在机制以及内在神经元成分所促进。由于最近的发现,可以预期在促进成体轴突再生和功能恢复方面将取得重大进展。