软骨素硫酸盐亚型的表达比较分析及其对胚胎期、成年期和损伤后大鼠脑轴突生长的抑制作用。
Comparative Analysis of the Expression of Chondroitin Sulfate Subtypes and Their Inhibitory Effect on Axonal Growth in the Embryonic, Adult, and Injured Rat Brains.
机构信息
Biomedical Research Institute, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.
Department of Physiology, Inha University College of Medicine, 100 Inha-ro, Michuhol-gu, Incheon, 22212, Republic of Korea.
出版信息
Tissue Eng Regen Med. 2021 Feb;18(1):165-178. doi: 10.1007/s13770-020-00295-z. Epub 2020 Sep 16.
BACKGROUND
Chondroitin sulfate glycosaminoglycans (CS-GAGs) are the primary inhibitory GAGs for neuronal growth after central nervous system (CNS) injury. However, the inhibitory or permissive activity of CS-GAG subtypes is controversial and depends on the physiological needs of CNS tissues. In this study, we investigated the characteristics and effects of CS-GAGs on axonal growth, which was isolated from the brain cortices of normal rat embryo at E18, normal adult rat brain and injured adult rat brain.
METHODS
Isolated CS-GAGs from embryo, normal adult, and injured adult rat brains were used for analyzing their effect on attachment and axonal growth using modified spot assay with dorsal root ganglion (DRG) explants and cerebellar granule neurons (CGNs). CS-GAGs were separated using high performance liquid chromatography (HPLC), and the subtypes of CS-GAGs were analyzed.
RESULTS
CS-GAGs of all three groups inhibited CGN attachment and axonal growth of DRGs. However, CS-GAGs of normal adult rat brain exhibited higher inhibitory activity than those of the other groups in both assays. When subtypes of CS-GAGs were analyzed using HPLC, CS-A (4S) was the most abundant in all three groups and found in largest amount in normal adult rat brain. In contrast, unsulfated CS (CS0) and CS-C (6S) were more abundant by 3-4-folds in E18 group than in the two adult groups.
CONCLUSION
When compared with the normal adult rat brain, injured rat brain showed relatively similar patterns to that of embryonic rat brain at E18 in the expression of CS subtypes and their inhibitory effect on axonal growth. This phenomenon could be due to differential expression of CS-GAGs subtypes causing decrease in the amount of CS-A and mature-type CS proteoglycan core proteins.
背景
硫酸软骨素糖胺聚糖（CS-GAGs）是中枢神经系统（CNS）损伤后神经元生长的主要抑制性 GAGs。然而，CS-GAG 亚型的抑制或许可活性存在争议，这取决于 CNS 组织的生理需求。在这项研究中，我们研究了 CS-GAGs 对轴突生长的特性和影响，CS-GAGs 是从 E18 正常大鼠胚胎大脑皮质、正常成年大鼠大脑和受伤成年大鼠大脑中分离出来的。
方法
使用改良的脊神经根节（DRG）外植体和小脑颗粒神经元（CGN）斑点分析，分析来自胚胎、正常成年和受伤成年大鼠大脑的分离 CS-GAGs 对附着和轴突生长的影响。CS-GAGs 用高效液相色谱（HPLC）分离，并分析 CS-GAGs 的亚型。
结果
三组 CS-GAGs 均抑制 CGN 附着和 DRG 轴突生长。然而，在两种测定中，正常成年大鼠脑 CS-GAGs 的抑制活性均高于其他两组。用 HPLC 分析 CS-GAGs 的亚型时，CS-A（4S）在三组中最为丰富，在正常成年大鼠脑中含量最大。相比之下，E18 组中未硫酸化的 CS（CS0）和 CS-C（6S）的含量比两组成年大鼠分别高出 3-4 倍。
结论
与正常成年大鼠脑相比，受伤大鼠脑在 CS 亚型的表达及其对轴突生长的抑制作用方面表现出与 E18 胚胎大鼠脑相似的模式。这种现象可能是由于 CS-GAGs 亚型的差异表达导致 CS-A 和成熟型 CS 蛋白聚糖核心蛋白的含量减少所致。
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