Cardiovascular & Metabolic Disease Center, College of Biomedical Science & Engineering, Inje University, Gimhae, Korea.
J Pineal Res. 2012 Jan;52(1):107-19. doi: 10.1111/j.1600-079X.2011.00925.x. Epub 2011 Aug 19.
The purpose of this study was to investigate the beneficial effects of endogenous and exogenous melatonin on functional recovery in an animal model of spinal cord injury (SCI). Eight-week-old male Sprague-Dawley (SD, 250-260 g) rats were used for contusion SCI surgery. All experimental groups were maintained under one of the following conditions: 12/12-hr light/dark (L/D) or 24:0-hr constant light (LL). Melatonin (10 mg/kg) was injected subcutaneously for 4 wk, twice daily (07:00, 19:00). Locomotor recovery, inducible nitric oxide synthase (iNOS), glial fibrillary acidic protein gene expression, and muscle atrophy-related genes, including muscle atrophy F-box (MAFbx) and muscle-specific ring-finger protein 1 (MuRF1) gene expression were evaluated. Furthermore, autophagic signaling such as Beclin-1 and LC3 protein expression was examined in the spinal cord and in skeletal muscle. The melatonin treatment resulted in increased hind-limb motor function and decreased iNOS mRNA expression in the L/D condition compared with the LL condition (P < 0.05), indicating that endogenous melatonin had neuroprotective effects. Furthermore, the MAFbx, MuRF1 mRNA level, and converted LC3 II protein expression were decreased in the melatonin-treated SCI groups under the LL (P < 0.05), possibly in response to the exogenous melatonin treatment. Therefore, it seems that both endogenous and exogenous melatonin contribute to neural recovery and to the prevention of skeletal muscle atrophy, promoting functional recovery after SCI. Finally, this study supports the benefit of endogenous melatonin and use of exogenous melatonin as a therapeutic intervention for SCI.
本研究旨在探讨内源性和外源性褪黑素对脊髓损伤（SCI）动物模型中功能恢复的有益作用。使用 8 周龄雄性 Sprague-Dawley（SD，250-260g）大鼠进行挫伤 SCI 手术。所有实验组均保持在以下条件之一：12/12 小时光照/黑暗（L/D）或 24：0 小时持续光照（LL）。褪黑素（10mg/kg）每天皮下注射两次，共 4 周（07：00，19：00）。评估运动功能恢复、诱导型一氧化氮合酶（iNOS）、神经胶质纤维酸性蛋白基因表达以及与肌肉萎缩相关的基因，包括肌肉萎缩 F 盒（MAFbx）和肌肉特异性环指蛋白 1（MuRF1）基因表达。此外，还在脊髓和骨骼肌中检查了自噬信号，如 Beclin-1 和 LC3 蛋白表达。褪黑素治疗可增加 L/D 条件下后肢运动功能，降低 iNOS mRNA 表达，与 LL 条件相比（P<0.05），表明内源性褪黑素具有神经保护作用。此外，在 LL 下，褪黑素治疗 SCI 组的 MAFbx、MuRF1 mRNA 水平和转化的 LC3 II 蛋白表达降低（P<0.05），可能是对外源性褪黑素治疗的反应。因此，内源性和外源性褪黑素似乎都有助于神经恢复和预防骨骼肌萎缩，促进 SCI 后的功能恢复。最后，本研究支持内源性褪黑素的益处，并将外源性褪黑素作为 SCI 的治疗干预措施。
