Howe Charles L, Adelson Jaimie D, Rodriguez Moses
Department of Neuroscience, Mayo Clinic College of Medicine, 200 First St SW, Rochester, MN 55905, USA.
Neurobiol Dis. 2007 Feb;25(2):354-9. doi: 10.1016/j.nbd.2006.10.001. Epub 2006 Nov 16.
Current evidence suggests that demyelination may be a necessary but not a sufficient condition for neurologic deficits associated with multiple sclerosis. Axon injury that occurs within the permissive environment of the demyelinated lesion is better correlated with functional deficits, but the mechanisms and cellular effectors of this injury are largely unknown. In an effort to identify potential axon injury mediators, we examined demyelination, motor function, and the number of spinal axons in perforin-deficient mice. Perforin is a critical molecular mediator of cytotoxic immunological injury and we hypothesized that genetic deletion of perforin expression would protect demyelinated axons. Indeed, we found that while perforin-deficient mice had considerable spinal cord demyelination 180 days after infection with Theiler's murine encephalomyelitis virus, such mice exhibited functional and axonal preservation comparable to non-demyelinated perforin-competent controls. We conclude that perforin-dependent effector cells such as cytotoxic T cells, gammadelta T cells, and natural killer cells may play a role in axon damage that is dependent upon but separable from demyelination.
目前的证据表明，脱髓鞘可能是与多发性硬化症相关的神经功能缺损的必要但非充分条件。在脱髓鞘病变的允许环境中发生的轴突损伤与功能缺损的相关性更强，但这种损伤的机制和细胞效应器在很大程度上尚不清楚。为了确定潜在的轴突损伤介质，我们研究了穿孔素缺陷小鼠的脱髓鞘、运动功能和脊髓轴突数量。穿孔素是细胞毒性免疫损伤的关键分子介质，我们假设穿孔素表达的基因缺失会保护脱髓鞘轴突。事实上，我们发现，虽然穿孔素缺陷小鼠在感染泰勒氏鼠脑脊髓炎病毒180天后脊髓有相当程度的脱髓鞘，但这些小鼠的功能和轴突保存情况与未脱髓鞘的穿孔素正常对照组相当。我们得出结论，穿孔素依赖的效应细胞，如细胞毒性T细胞、γδT细胞和自然杀伤细胞，可能在依赖于脱髓鞘但与之可分离的轴突损伤中起作用。
