脊髓损伤(SCI)后的轴突再生受到中枢神经系统(CNS)中几种类型的抑制性细胞外分子的抑制,包括硫酸软骨素蛋白聚糖(CSPGs),它们也是神经周网(PNN)的组成部分。七叶鱼的轴突在SCI后再生,即使它们的脊髓含有CSPG,它们的神经元被PNN包裹。以前,我们发现,在七叶鱼脊髓横断2周后,CSPGs在病变部位的表达增加,此后,降低到受伤前的水平10周。用软骨素酶ABC(ChABC)酶消化病变部位的CSPGs可增强SCI后的轴突再生并减少逆行神经元死亡。Lecticans(aggrecan,versican,Neurocan,和brevican)是中枢神经系统中主要的CSPG家族。以前,我们克隆了一个cDNA片段,该片段位于七头鱼的最保守的连接域中,并发现了七头鱼神经胶质和神经元中广泛表达的凝集素mRNAs。由于缺乏对下颚脊椎动物的严格的一对一矫形,这四个七叶鱼的名字简称为A,B,C,和D.使用区分这四个调子的探针,我们现在表明,它们都在神经胶质和神经元中表达,但表达水平不同。在胚胎和幼体早期的表达水平相对较高,逐渐减少,并在成年人中再次上调。B和D的减少大于A和C的减少。SCI后,B和D的mRNA水平急剧增加。LecticanD保持上调至少10周。多个细胞,包括胶质细胞,神经元,室管膜细胞和小胶质细胞/巨噬细胞,SCI后在外周区和病变中心表达凝集素mRNA。因此,就像哺乳动物一样,七叶鱼可能在发育早期参与轴突引导和神经可塑性。此外,神经元,glia,室管膜细胞,和小胶质细胞/巨噬细胞,是SCI后神经胶质瘢痕形成过程中CSPG增加的原因。
Axon regrowth after spinal cord injury (SCI) is inhibited by several types of inhibitory extracellular molecules in the central nervous system (CNS), including chondroitin sulfate proteoglycans (CSPGs), which also are components of perineuronal nets (PNNs). The axons of lampreys regenerate following SCI, even though their spinal cords contain CSPGs, and their neurons are enwrapped by PNNs. Previously, we showed that by 2 weeks after spinal cord transection in the lamprey, expression of CSPGs increased in the lesion site, and thereafter, decreased to pre-injury levels by 10 weeks. Enzymatic digestion of CSPGs in the lesion site with chondroitinase ABC (ChABC) enhanced axonal regeneration after SCI and reduced retrograde neuronal death.
Lecticans (aggrecan, versican, neurocan, and brevican) are the major CSPG family in the CNS. Previously, we cloned a cDNA fragment that lies in the most conserved link-domain of the lamprey lecticans and found that lectican mRNAs are expressed widely in lamprey glia and neurons. Because of the lack of strict one-to-one orthology with the jawed vertebrate lecticans, the four lamprey
lecticans were named simply A, B, C, and D. Using probes that distinguish these four lecticans, we now show that they all are expressed in glia and neurons but at different levels. Expression levels are relatively high in embryonic and early larval stages, gradually decrease, and are upregulated again in adults. Reductions of
lecticans B and D are greater than those of A and C. Levels of mRNAs for
lecticans B and D increased dramatically after SCI. Lectican D remained upregulated for at least 10 weeks. Multiple cells, including glia, neurons, ependymal cells and microglia/macrophages, expressed lectican mRNAs in the peripheral zone and lesion center after SCI. Thus, as in mammals, lamprey
lecticans may be involved in axon guidance and neuroplasticity early in development. Moreover, neurons, glia, ependymal cells, and microglia/macrophages, are responsible for the increase in CSPGs during the formation of the glial scar after SCI.