Beneficial effects of endogenous and exogenous melatonin on neural reconstruction and functional recovery in an animal model of spinal cord injury

Authors

  • Sookyoung Park,

    Corresponding author
    1. Cardiovascular & Metabolic Disease Center, College of Biomedical Science & Engineering, Inje University, Gimhae, Korea
      Address reprint requests to Yonggeung Hong, Department of Rehabilitation Science in Interdisciplinary PhD Program, College of Biomedical Science & Engineering, Inje University, 607 Obang-dong, Gimhae 621-749 (to Gyeongnam 621-749), Korea; Kyu-Tae Chang, National Primate Research Center (NPRC), Korea Research Institute of Bioscience and Biotechnology (KRIBB), Ochang 363-883 (to Chungbuk 363-883), Korea
      E-mails: yonghong@inje.ac.kr; changkt@kribb.re.kr
    Search for more papers by this author
  • Sang-Kil Lee,

    Corresponding author
    1. Cardiovascular & Metabolic Disease Center, College of Biomedical Science & Engineering, Inje University, Gimhae, Korea
      Address reprint requests to Yonggeung Hong, Department of Rehabilitation Science in Interdisciplinary PhD Program, College of Biomedical Science & Engineering, Inje University, 607 Obang-dong, Gimhae 621-749 (to Gyeongnam 621-749), Korea; Kyu-Tae Chang, National Primate Research Center (NPRC), Korea Research Institute of Bioscience and Biotechnology (KRIBB), Ochang 363-883 (to Chungbuk 363-883), Korea
      E-mails: yonghong@inje.ac.kr; changkt@kribb.re.kr
    Search for more papers by this author
  • Kanghui Park,

    Corresponding author
    1. Department of Rehabilitation Science in Interdisciplinary PhD Program, College of Biomedical Science & Engineering, Inje University, Gimhae, Korea
      Address reprint requests to Yonggeung Hong, Department of Rehabilitation Science in Interdisciplinary PhD Program, College of Biomedical Science & Engineering, Inje University, 607 Obang-dong, Gimhae 621-749 (to Gyeongnam 621-749), Korea; Kyu-Tae Chang, National Primate Research Center (NPRC), Korea Research Institute of Bioscience and Biotechnology (KRIBB), Ochang 363-883 (to Chungbuk 363-883), Korea
      E-mails: yonghong@inje.ac.kr; changkt@kribb.re.kr
    Search for more papers by this author
  • Youngjeon Lee,

    1. Department of Rehabilitation Science in Interdisciplinary PhD Program, College of Biomedical Science & Engineering, Inje University, Gimhae, Korea
    Search for more papers by this author
  • Yunkyung Hong,

    1. Department of Rehabilitation Science in Interdisciplinary PhD Program, College of Biomedical Science & Engineering, Inje University, Gimhae, Korea
    Search for more papers by this author
  • Seunghoon Lee,

    1. Department of Rehabilitation Science in Interdisciplinary PhD Program, College of Biomedical Science & Engineering, Inje University, Gimhae, Korea
    Search for more papers by this author
  • Je-Cheol Jeon,

    1. Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju, Korea
    Search for more papers by this author
  • Joo-Heon Kim,

    1. Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju, Korea
    Search for more papers by this author
  • Sang-Rae Lee,

    1. National Primate Research Center (NPRC), Korea Research Institute of Bioscience and Biotechnology (KRIBB), Ochang, Korea
    Search for more papers by this author
  • Kyu-Tae Chang,

    1. National Primate Research Center (NPRC), Korea Research Institute of Bioscience and Biotechnology (KRIBB), Ochang, Korea
    Search for more papers by this author
  • Yonggeun Hong

    1. Cardiovascular & Metabolic Disease Center, College of Biomedical Science & Engineering, Inje University, Gimhae, Korea
    2. Department of Rehabilitation Science in Interdisciplinary PhD Program, College of Biomedical Science & Engineering, Inje University, Gimhae, Korea
    3. National Primate Research Center (NPRC), Korea Research Institute of Bioscience and Biotechnology (KRIBB), Ochang, Korea
    Search for more papers by this author

  • These authors contributed equally to this work.

Address reprint requests to Yonggeung Hong, Department of Rehabilitation Science in Interdisciplinary PhD Program, College of Biomedical Science & Engineering, Inje University, 607 Obang-dong, Gimhae 621-749 (to Gyeongnam 621-749), Korea; Kyu-Tae Chang, National Primate Research Center (NPRC), Korea Research Institute of Bioscience and Biotechnology (KRIBB), Ochang 363-883 (to Chungbuk 363-883), Korea
E-mails: yonghong@inje.ac.kr; changkt@kribb.re.kr

Abstract

Abstract:  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 (< 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 (< 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.

Ancillary