Oppenheim R W, Houenou L J, Johnson J E, Lin L F, Li L, Lo A C, Newsome A L, Prevette D M, Wang S
Department of Neurobiology and Anatomy, Bowman Gray School of Medicine, Wake Forest University, Winston Salem, North Carolina 27157.
Nature. 1995 Jan 26;373(6512):344-6. doi: 10.1038/373344a0.
During normal development of the vertebrate nervous system, large numbers of neurons in the central and peripheral nervous system undergo naturally occurring cell death. For example, about half of all spinal motor neurons die over a period of a few days in developing avian, rat and mouse embryos. Previous studies have shown that extracts from muscle and brain, secreted factors from glia, as well as several growth factors and neurotrophic agents, including muscle-derived factors, can promote the survival of developing motor neurons in vitro and in vivo. But because neurotrophins and other known trophic agents administered alone or in combination are insufficient to rescue all developing motor neurons from cell death, other neurotrophic molecules are probably essential for the survival and differentiation of motor neurons. Here we report that glial-cell-line-derived neurotrophic factor (GDNF), a potent neurotrophic factor that enhances survival of mammalian midbrain dopaminergic neurons, rescues developing avian motor neurons from natural programmed cell death in vivo and promotes the survival of enriched populations of cultured motor neurons. Furthermore, treatment with this agent in vivo also prevents the induced death and atrophy of both avian and mouse spinal motor neurons following peripheral axotomy.
在脊椎动物神经系统的正常发育过程中，中枢神经系统和周围神经系统中的大量神经元会自然发生细胞死亡。例如，在鸡、大鼠和小鼠胚胎发育过程中，约一半的脊髓运动神经元会在几天内死亡。先前的研究表明，肌肉和脑提取物、胶质细胞分泌因子以及几种生长因子和神经营养因子，包括肌肉衍生因子，在体外和体内均可促进发育中的运动神经元存活。但是，由于单独或联合使用神经营养因子和其他已知的营养因子不足以挽救所有发育中的运动神经元免于细胞死亡，因此其他神经营养分子可能对运动神经元的存活和分化至关重要。在此我们报告，胶质细胞系衍生的神经营养因子（GDNF）是一种强大的神经营养因子，可增强哺乳动物中脑多巴胺能神经元的存活，它能在体内挽救发育中的鸡运动神经元免于自然程序性细胞死亡，并促进培养的运动神经元富集群体的存活。此外，在体内用这种因子治疗还可防止鸡和小鼠脊髓运动神经元在周围神经切断后发生诱导性死亡和萎缩。
