title: Beneficial effects of endogenous and exogenous melatonin on neural reconstruction and functional recovery in an animal model of spinal cord injury.
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 (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.
authors.affiliation: Cardiovascular & Metabolic Disease Center, College of Biomedical Science & Engineering, Inje University, Gimhae, Korea.
authors.forename: Sookyoung
authors.initials: S
authors.lastname: Park
authors.forename: Sang-Kil
authors.initials: SK
authors.lastname: Lee
authors.forename: Kanghui
authors.initials: K
authors.lastname: Park
authors.forename: Youngjeon
authors.initials: Y
authors.lastname: Lee
authors.forename: Yunkyung
authors.initials: Y
authors.lastname: Hong
authors.forename: Seunghoon
authors.initials: S
authors.lastname: Lee
authors.forename: Je-Cheol
authors.initials: JC
authors.lastname: Jeon
authors.forename: Joo-Heon
authors.initials: JH
authors.lastname: Kim
authors.forename: Sang-Rae
authors.initials: SR
authors.lastname: Lee
authors.forename: Kyu-Tae
authors.initials: KT
authors.lastname: Chang
authors.forename: Yonggeun
authors.initials: Y
authors.lastname: Hong
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001343:Autophagy / Q000187:drug effects; D015153:Blotting, Western; D001835:Body Weight; D004195:Disease Models, Animal; D008297:Male; D008550:Melatonin / Q000378:metabolism* / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects*; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D009133:Muscular Atrophy / Q000378:metabolism; D018696:Neuroprotective Agents / Q000378:metabolism / Q000494:pharmacology; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044843:SKP Cullin F-Box Protein Ligases / Q000235:genetics / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000188:drug therapy / Q000378:metabolism*; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism
chemical_list: D009124:Muscle Proteins; D018696:Neuroprotective Agents; D000070584:Tripartite Motif Proteins; D052247:Nitric Oxide Synthase Type II; C486692:Fbxo32 protein, rat; D044843:SKP Cullin F-Box Protein Ligases; C499086:Trim63 protein, rat; D044767:Ubiquitin-Protein Ligases; D008550:Melatonin