Shen Wen-Yuan, Fu Xuan-Hao, Cai Jun, Li Wen-Chang, Fan Bao-You, Pang Yi-Lin, Zhao Chen-Xi, Abula Muhtidir, Kong Xiao-Hong, Yao Xue, Feng Shi-Qing
International Science and Technology Cooperation Base of Spinal Cord Injury, Tianjin Key Laboratory of Spine and Spinal Cord, Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin, China.
Tianjin Medicine and Health Research Center, Tianjin Institute of Medical & Pharmaceutical Sciences, Tianjin, China.
Neural Regen Res. 2022 Jun;17(6):1334-1342. doi: 10.4103/1673-5374.327360.
Zebrafish are an effective vertebrate model to study the mechanisms underlying recovery after spinal cord injury. The subacute phase after spinal cord injury is critical to the recovery of neurological function, which involves tissue bridging and axon regeneration. In this study, we found that zebrafish spontaneously recovered 44% of their swimming ability within the subacute phase (2 weeks) after spinal cord injury. During this period, we identified 7762 differentially expressed genes in spinal cord tissue: 2950 were up-regulated and 4812 were down-regulated. These differentially expressed genes were primarily concentrated in the biological processes of the respiratory chain, axon regeneration, and cell-component morphogenesis. The genes were also mostly involved in the regulation of metabolic pathways, the cell cycle, and gene-regulation pathways. We verified the gene expression of two differentially expressed genes, clasp2 up-regulation and h1m down-regulation, in zebrafish spinal cord tissue in vitro. Pathway enrichment analysis revealed that up-regulated clasp2 functions similarly to microtubule-associated protein, which is responsible for axon extension regulated by microtubules. Down-regulated h1m controls endogenous stem cell differentiation after spinal cord injury. This study provides new candidate genes, clasp2 and h1m, as potential therapeutic intervention targets for spinal cord injury repair by neuroregeneration. All experimental procedures and protocols were approved by the Animal Ethics Committee of Tianjin Institute of Medical & Pharmaceutical Sciences (approval No. IMPS-EAEP-Q-2019-02) on September 24, 2019.
斑马鱼是研究脊髓损伤后恢复机制的一种有效脊椎动物模型。脊髓损伤后的亚急性期对神经功能的恢复至关重要，这涉及组织桥接和轴突再生。在本研究中，我们发现斑马鱼在脊髓损伤后的亚急性期（2周）内自发恢复了44%的游泳能力。在此期间，我们在脊髓组织中鉴定出7762个差异表达基因：2950个上调，4812个下调。这些差异表达基因主要集中在呼吸链、轴突再生和细胞成分形态发生的生物学过程中。这些基因还大多参与代谢途径、细胞周期和基因调控途径的调节。我们在体外验证了斑马鱼脊髓组织中两个差异表达基因clasp2上调和h1m下调的基因表达。通路富集分析显示，上调的clasp2的功能类似于微管相关蛋白，后者负责微管调节的轴突延伸。下调的h1m控制脊髓损伤后内源性干细胞的分化。本研究提供了新的候选基因clasp2和h1m，作为通过神经再生修复脊髓损伤的潜在治疗干预靶点。所有实验程序和方案均于2019年9月24日获得天津医学与制药科学研究所动物伦理委员会批准（批准号：IMPS-EAEP-Q-2019-02）。
