Center for Molecular Neurobiology Hamburg, University Hospital Hamburg-Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany.
Neuroscience. 2013 Nov 12;252:1-12. doi: 10.1016/j.neuroscience.2013.07.067. Epub 2013 Aug 7.
It has been shown that the X-chromosome-linked neural cell adhesion molecule L1 plays a beneficial role in regeneration after spinal cord injury (SCI) in young adult rodents when applied in various molecular and cellular forms. In an attempt to further characterize the multiple functions of L1 after severe SCI we analyzed locomotor functions and measured axonal regrowth/sprouting and sparing, glial scarring, and synaptic remodeling at 6 weeks after severe spinal cord compression injury at the T7-9 levels of L1-deficient mice (L1-/y) and their wild-type (L1+/y) littermates, as well as mice that overexpress L1 under the control of the neuron-specific Thy-1 promoter (L1tg) and their wild-type littermates (L1+/+). No differences were found in the locomotor scale score and single frame motion analysis between L1-/y and L1+/y mice during 6 weeks after SCI, most likely due to the very low expression of L1 in the adult spinal cord of wild-type mice. L1tg mice, however, showed better locomotor recovery than their L1+/+ littermates, being associated with enhanced numbers of catecholaminergic axons in the lumbar spinal cord, but not of cholinergic, GABAergic or glutamatergic terminals around motoneuron cell bodies in the lumbar spinal cord. Additionally, no difference between L1tg and L1+/+ mice was detectable in dieback of corticospinal tract axons. Neuronal L1 overexpression did not influence the size of the glial fibrillary acidic protein-immunoreactive astrocytic scar 6 weeks after injury. We conclude that neuronal overexpression of L1 improves functional recovery from SCI by increasing catecholaminergic axonal regrowth/sprouting and/or sparing of severed axons without affecting the glial scar size.
已经表明，X 染色体连锁的神经细胞粘附分子 L1 在各种分子和细胞形式下发挥有益作用，可促进成年啮齿动物脊髓损伤（SCI）后的再生。在尝试进一步描述严重 SCI 后 L1 的多种功能时，我们分析了运动功能，并测量了 6 周后严重脊髓压迫损伤后 T7-9 水平的 L1 缺陷型（L1-/y）和野生型（L1+/y）同窝鼠以及过表达 L1 的神经元特异性 Thy-1 启动子（L1tg）及其野生型同窝鼠（L1+/+）中的轴突再生/发芽和保留、胶质瘢痕形成和突触重塑。在 SCI 后 6 周内，L1-/y 和 L1+/y 小鼠之间在运动量表评分和单帧运动分析方面没有差异，这很可能是由于野生型小鼠成年脊髓中 L1 的表达非常低。然而，L1tg 小鼠的运动恢复比其 L1+/+同窝鼠更好，这与腰髓中儿茶酚胺能轴突数量增加有关，但与腰髓运动神经元细胞体周围的胆碱能、GABA 能或谷氨酸能终末无关。此外，L1tg 和 L1+/+ 小鼠之间在皮质脊髓束轴突退变方面没有差异。神经元 L1 的过表达不会影响损伤后 6 周时胶质纤维酸性蛋白免疫反应性星形胶质瘢痕的大小。我们得出结论，神经元过表达 L1 通过增加儿茶酚胺能轴突的再生/发芽和/或保留被切断的轴突来改善 SCI 的功能恢复，而不会影响神经胶质瘢痕的大小。
