Takeda Akihito, Okada Soichiro, Funakoshi Kengo
Department of Neuroanatomy, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
Brain Res. 2017 Oct 15;1673:23-29. doi: 10.1016/j.brainres.2017.08.004. Epub 2017 Aug 8.
Chondroitin sulfate proteoglycans produced in glial scar tissue are a major inhibitory factor for axonal regeneration after central nervous system injury in mammals. The inhibition is largely due to chondroitin sulfates, whose effects differ according to the sulfation pattern. In contrast to mammals, fish nerves spontaneously regenerate beyond the scar tissue after spinal cord injury, although the mechanisms that allow for axons to pass through the scar are unclear. Here, we used immunohistochemistry to examine the expression of two chondroitin sulfates with different sulfation variants at the lesion site in goldfish spinal cord. The intact spinal cord was immunoreactive for both chondroitin sulfate-A (CS-A) and chondroitin sulfate-C (CS-C), and CS-A immunoreactivity overlapped extensively with glial processes positive for glial fibrillary acidic protein. At 1week after inducing the spinal lesion, CS-A immunoreactivity was observed in the cell bodies and extracellular matrix, as well as in glial processes surrounding the lesion center. At 2weeks after the spinal lesion, regenerating axons entering the lesion center overtook the CS-A abundant area. In contrast, at 1week after lesion induction, CS-C immunoreactivity was significantly decreased, and at 2weeks after lesion induction, CS-C immunoreactivity was observed along the regenerating axons entering the lesion center. The present findings suggest that after spinal cord injury in goldfish, chondroitin sulfate proteoglycans are deposited in the extracellular matrix at the lesion site but do not form an impenetrable barrier to the growth of regenerating axons.
神经胶质瘢痕组织中产生的硫酸软骨素蛋白聚糖是哺乳动物中枢神经系统损伤后轴突再生的主要抑制因子。这种抑制主要归因于硫酸软骨素，其作用因硫酸化模式而异。与哺乳动物不同，鱼类神经在脊髓损伤后能自发地越过瘢痕组织再生，尽管轴突穿过瘢痕的机制尚不清楚。在这里，我们使用免疫组织化学方法检测了金鱼脊髓损伤部位两种具有不同硫酸化变体的硫酸软骨素的表达情况。完整的脊髓对硫酸软骨素A（CS-A）和硫酸软骨素C（CS-C）均有免疫反应，且CS-A免疫反应性与胶质纤维酸性蛋白阳性的神经胶质突起广泛重叠。在诱导脊髓损伤后1周，在细胞体、细胞外基质以及损伤中心周围的神经胶质突起中均观察到CS-A免疫反应性。在脊髓损伤后2周，进入损伤中心的再生轴突超过了CS-A丰富的区域。相比之下，在损伤诱导后1周，CS-C免疫反应性显著降低，而在损伤诱导后2周，在进入损伤中心的再生轴突上观察到CS-C免疫反应性。目前的研究结果表明，金鱼脊髓损伤后，硫酸软骨素蛋白聚糖沉积在损伤部位的细胞外基质中，但不会对再生轴突的生长形成不可穿透的屏障。
