The chondroitin sulfate proteoglycans neurocan, brevican, phosphacan, and versican are differentially regulated following spinal cord injury
The chondroitin sulfate proteoglycans neurocan, brevican, phosphacan, and versican are differentially regulated following spinal cord injury
复制标题
DOI：
10.1016/s0014-4886(03)00087-6
复制
发表时间：
2003-08-01
影响因子：
5.3
通讯作者：
Tuszynski, MH
中科院分区：
文献类型：
--
作者：
Jones, LL;Margolis, RU;Tuszynski, MH
硫酸软骨素蛋白聚糖（CSPG）是细胞外基质（ECM）分子，广泛表达于整个发育和成人CNS。体外研究表明它们有限制神经突生长的潜力，并且据信CSPG还抑制体内中枢神经系统损伤后的轴突再生。先前的研究表明，脊髓损伤后CSPGs通常上调，最近的报道已经开始确定可能在限制轴突再生中发挥主导作用的单个蛋白多糖。目前的研究系统地研究了四种pupectin抑制CSPG CNS损伤后的扩展沉积模式，这些CSPG以前在体内没有被广泛研究：neurocan，brevican，phosphacan和versican。脊髓损伤后，neurocan，brevican和versican免疫标记在损伤部位周围的脊髓实质中在几天内增加，并在2周时达到峰值。Neurocan和versican在伤后4周持续升高，短蛋白聚糖表达持续至少2个月。另一方面，磷酸蛋白聚糖免疫标记在损伤后立即在同一区域下降，但后来恢复，然后在2个月后达到峰值。结合胶质细胞酸性蛋白（GFAP）免疫组化和原位杂交表明，GFAP星形胶质细胞构成了脊髓损伤后神经肽的生产来源。因此，几个CSPG家族成员的产生受到脊髓损伤的不同影响，总体上建立了在损伤后持续长达2个月的富含CSPG的基质。减少CSPG表达以增强再生的策略的优化可能需要在损伤后的较长时间内靶向几个不同的家族成员。(C)2003 Elsevier Science（美国）。All rights reserved.
Chondroitin sulfate proteoglycans (CSPGs) are extracellular matrix (ECM) molecules that are widely expressed throughout the developing and adult CNS. In vitro studies demonstrate their potential to restrict neurite outgrowth, and it is believed that CSPGs also inhibit axonal regeneration after CNS injury in vivo. Previous studies demonstrated that CSPGs are generally upregulated after spinal cord injury, and more recent reports have begun to identify individual proteoglycans that may play dominant roles in limiting axonal regeneration. The current study systematically examined the extended deposition patterns after CNS injury of four putatively inhibitory CSPGs that have not been extensively investigated previously in vivo: neurocan, brevican, phosphacan, and versican. After spinal cord injury, neurocan, brevican, and versican immunolabeling increased within days in injured spinal cord parenchyma surrounding the lesion site and peaked at 2 weeks. Neurocan and versican were persistently elevated for 4 weeks postinjury, and brevican expression persisted for at least 2 months. On the other hand, phosphacan immunolabeling decreased in the same region immediately following injury but later recovered and then peaked after 2 months. Combined glial fibrillary acidic protein (GFAP) immunohistochemistry and in situ hybridization demonstrated that GFAP astrocytes constituted a source of neurocan production after spinal cord injury. Thus, the production of several CSPG family members is differentially affected by spinal cord injury, overall establishing a CSPG-rich matrix that persists for up to 2 months following injury. Optimization of strategies to reduce CSPG expression to enhance regeneration may need to target several different family members over an extended period following injury. (C) 2003 Elsevier Science (USA). All rights reserved.