Dubois-Dauphin M, Frankowski H, Tsujimoto Y, Huarte J, Martinou J C
Department of Physiology, University Medical Center, Geneva, Switzerland.
Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3309-13. doi: 10.1073/pnas.91.8.3309.
In vitro, the overexpression of the bcl-2 protooncogene in cultured neurons has been shown to prevent apoptosis induced by neurotrophic factor deprivation. We have generated transgenic mice overexpressing the Bcl-2 protein in neurons, including motoneurons of the facial nucleus. We have tested whether Bcl-2 could protect these motoneurons from experimentally induced cell death in new born mice. To address this question, we performed unilateral lesion of the facial nerve of wild-type and transgenic 2-day-old mice. In wild-type mice, the lesioned nerve and the corresponding motoneuron cell bodies in the facial nucleus underwent rapid degeneration. In contrast, in transgenic mice, facial motoneurons survived axotomy. Not only their cell bodies but also their axons were protected up to the lesion site. These results demonstrate that in vivo Bcl-2 protects neonatal motoneurons from degeneration after axonal injury. A better understanding of the mechanisms by which Bcl-2 prevents neuronal cell death in vivo could lead to the development of strategies for the treatment of motoneuron degenerative diseases.
在体外实验中，已证明培养的神经元中bcl - 2原癌基因的过表达可防止因神经营养因子剥夺诱导的细胞凋亡。我们已培育出在神经元（包括面神经核的运动神经元）中过表达Bcl - 2蛋白的转基因小鼠。我们测试了Bcl - 2是否能保护这些运动神经元免受新生小鼠实验性诱导的细胞死亡。为解决这个问题，我们对野生型和转基因2日龄小鼠的面神经进行了单侧损伤。在野生型小鼠中，受损神经和面神经核中相应的运动神经元细胞体迅速退化。相比之下，在转基因小鼠中，面部运动神经元在轴突切断后存活下来。不仅它们的细胞体，而且它们的轴突都受到保护直至损伤部位。这些结果表明，在体内Bcl - 2可保护新生运动神经元免受轴突损伤后的退化。更好地理解Bcl - 2在体内防止神经元细胞死亡的机制可能会带来治疗运动神经元退行性疾病策略的发展。
