Zhang Guixin, Jin Li-Qing, Rodemer William, Hu Jianli, Root Zachary D, Medeiros Daniel M, Selzer Michael E
Shriners Hospitals Pediatric Research Center (Center for Neural Repair and Rehabilitation), Department of Neural Sciences, Philadelphia, PA, United States.
Department of Ecology and Evolutionary Biology, University of Colorado, Boulder, CO, United States.
Front Mol Neurosci. 2022 Jun 27;15:918871. doi: 10.3389/fnmol.2022.918871. eCollection 2022.
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. (aggrecan, versican, neurocan, and brevican) are the major 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.
脊髓损伤（SCI）后轴突再生受到中枢神经系统（CNS）中几种抑制性细胞外分子的抑制，包括硫酸软骨素蛋白聚糖（CSPG），其也是神经元周围网（PNN）的组成部分。七鳃鳗的轴突在脊髓损伤后能够再生，尽管它们的脊髓含有CSPG，并且其神经元被PNN包裹。此前，我们发现七鳃鳗脊髓横断后2周，损伤部位CSPG的表达增加，此后，到10周时降至损伤前水平。用软骨素酶ABC（ChABC）对损伤部位的CSPG进行酶解可增强脊髓损伤后的轴突再生并减少逆行性神经元死亡。（聚集蛋白聚糖、多功能蛋白聚糖、神经蛋白聚糖和短蛋白聚糖）是中枢神经系统中的主要家族。此前，我们克隆了一个位于七鳃鳗凝集素最保守连接域的cDNA片段，并发现凝集素mRNA在七鳃鳗的神经胶质细胞和神经元中广泛表达。由于与有颌脊椎动物凝集素缺乏严格的一对一的直系同源性，这四种七鳃鳗凝集素被简单地命名为A、B、C和D。使用区分这四种凝集素的探针，我们现在表明它们都在神经胶质细胞和神经元中表达，但表达水平不同。在胚胎期和幼体早期表达水平相对较高，随后逐渐下降，并在成体中再次上调。凝集素B和D的减少幅度大于A和C。脊髓损伤后凝集素B和D的mRNA水平显著增加。凝集素D至少在10周内持续上调。包括神经胶质细胞、神经元、室管膜细胞和小胶质细胞/巨噬细胞在内的多种细胞在脊髓损伤后的外周区和损伤中心表达凝集素mRNA。因此，与哺乳动物一样，七鳃鳗凝集素可能在发育早期参与轴突导向和神经可塑性。此外，神经元、神经胶质细胞、室管膜细胞和小胶质细胞/巨噬细胞在脊髓损伤后胶质瘢痕形成过程中导致CSPG增加。
