Murphy J A, Franklin T B, Rafuse V F, Clarke D B
Neuron Survival and Regeneration Laboratory, Faculty of Medicine, Dalhousie University, 5850 College Street, Halifax, Nova Scotia, Canada B3H 1X5.
Mol Cell Neurosci. 2007 Oct;36(2):280-92. doi: 10.1016/j.mcn.2007.07.006. Epub 2007 Jul 24.
Retinal ganglion cells (RGCs) undergo apoptotic death in predictable time-dependant manners during development and as a consequence of injury. Recently, synthetic neural cell adhesion molecule (NCAM) agonists have been shown to provide neuroprotective support. Within the adult mouse retina, NCAM has been localized on all neurons and glia; however, no functional role has been determined. Using adult NCAM-/- mice, we directly tested the potential influence of NCAM on neuron survival in vivo and observed that, in NCAM-/- retinas, RGC densities are greater, RGC loss after injury is earlier and target tissue significantly influences adult RGC survival, all in contrast to wild-type retinas. Collectively, our results indicate that NCAM may play a vital role in regulating the developmental change in the effectiveness of local versus target-derived RGC trophic support and that, in the adult, endogenous NCAM influences the total number of CNS neurons and their survival following injury.
视网膜神经节细胞(RGCs)在发育过程中以及作为损伤的结果,会以可预测的时间依赖性方式经历凋亡死亡。最近,合成神经细胞粘附分子(NCAM)激动剂已被证明能提供神经保护支持。在成年小鼠视网膜中,NCAM已定位在所有神经元和神经胶质细胞上;然而,尚未确定其功能作用。使用成年NCAM基因敲除小鼠,我们直接测试了NCAM对体内神经元存活的潜在影响,并观察到,在NCAM基因敲除的视网膜中,RGC密度更高,损伤后RGC损失更早,且靶组织显著影响成年RGC的存活,所有这些都与野生型视网膜形成对比。总体而言,我们的结果表明,NCAM可能在调节局部与靶源RGC营养支持有效性的发育变化中起关键作用,并且在成年期,内源性NCAM会影响中枢神经系统神经元的总数及其损伤后的存活。