Department of Orthopaedics, First Affiliated Hospital, China Medical University, Shenyang, People's Republic of China.
Laboratory Teaching Center, School of Forensic Medicine, China Medical University, Shenyang, People's Republic of China.
Cell Calcium. 2018 Dec;76:122-128. doi: 10.1016/j.ceca.2018.11.003. Epub 2018 Nov 13.
Spinal cord injury (SCI) causes long-term disability and has no effective clinical treatment. After SCI, extracellular adenosine triphosphate (ATP) leads to an influx of extracellular Ca, and this Ca overload causes neuronal toxicosis and apoptosis. The biological functions of leptin have been widely investigated in the central nervous system. In this study, we discovered that the administration of leptin could improve locomotor recovery following SCI. The aim of this study was to determine the neuroprotective mechanism of leptin in vivo and in vitro. The neuronal apoptosis and Ca imaging signal induced by ATP were suppressed by leptin, due to elevated caveolin-1 expression. In vivo two-photon observations revealed that leptin reduced the neuronal Ca imaging signal in the exposed spinal cords of live Thy1-YFP mice. In conclusion, leptin promotes locomotor functional recovery and suppresses neuronal impairment after SCI, suggesting that leptin has a promising clinical therapeutic value for treatment of SCI.
脊髓损伤(SCI)导致长期残疾,目前尚无有效的临床治疗方法。SCI 后,细胞外三磷酸腺苷(ATP)导致细胞外 Ca 内流,这种 Ca 超载导致神经元毒性和细胞凋亡。瘦素在中枢神经系统中的生物学功能已被广泛研究。在这项研究中,我们发现瘦素的给药可以改善 SCI 后的运动功能恢复。本研究的目的是确定瘦素在体内和体外的神经保护机制。瘦素通过上调窖蛋白-1 的表达来抑制 ATP 诱导的神经元凋亡和 Ca 成像信号。体内双光子观察显示,瘦素减少了活体 Thy1-YFP 小鼠暴露脊髓中的神经元 Ca 成像信号。总之,瘦素促进 SCI 后运动功能的恢复并抑制神经元损伤,提示瘦素具有治疗 SCI 的潜在临床治疗价值。