Center for Neuroscience, Shantou University Medical College, 22 Xin Ling Road, Shantou, Guangdong, 515041, China.
Medical School, Jiangnan University, 1800 Li Hu Road, Wuxi, Jiangsu, 214122, China.
Mol Neurobiol. 2018 Jan;55(1):859-878. doi: 10.1007/s12035-016-0254-z. Epub 2017 Jan 9.
Tacrine is a small organic compound that was discovered to mimic the functions of the neural cell adhesion molecule L1 by promoting the cognate functions of L1 in vitro, such as neuronal survival, neuronal migration, neurite outgrowth, and myelination. Based on studies indicating that L1 enhances functional recovery in different central and peripheral nervous system disease paradigms of rodents, it deemed interesting to investigate the beneficial role of tacrine in the attractive zebrafish animal model, by evaluating functional recovery after spinal cord injury. To this aim, larval and adult zebrafish were exposed to tacrine treatment after spinal cord injury and monitored for locomotor recovery and axonal regrowth. Tacrine promoted the rapid recovery of locomotor activities in both larval and adult zebrafish, enhanced regrowth of severed axons and myelination, and reduced astrogliosis in the spinal cords. Tacrine treatment upregulated the expression of L1.1 (a homolog of the mammalian recognition molecule L1) and enhanced the L1.1-mediated intracellular signaling cascades in the injured spinal cords. These observations lead to the hope that, in combination with other therapeutic approaches, this old drug may become a useful reagent to ameliorate the deficits resulting from acute and chronic injuries of the mammalian nervous system.
他克林是一种小分子有机化合物，被发现可通过促进 L1 的同源功能（如神经元存活、神经元迁移、突起生长和髓鞘形成）来模拟神经细胞黏附分子 L1 的功能。基于研究表明 L1 可增强啮齿动物不同中枢和周围神经系统疾病模型中的功能恢复，因此研究他克林在有吸引力的斑马鱼动物模型中的有益作用（通过评估脊髓损伤后的功能恢复）是很有趣的。为此，在脊髓损伤后，幼鱼和成年斑马鱼暴露于他克林处理，并监测运动功能的恢复和轴突再生。他克林促进了幼鱼和成年斑马鱼运动活动的快速恢复，增强了切断轴突的再生和髓鞘形成，并减少了脊髓中的星形胶质细胞增生。他克林处理上调了 L1.1（哺乳动物识别分子 L1 的同源物）的表达，并增强了损伤脊髓中的 L1.1 介导的细胞内信号级联反应。这些观察结果使人们希望，这种旧药物与其他治疗方法相结合，可能成为改善哺乳动物神经系统急性和慢性损伤所致缺陷的有用试剂。
