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.

Beneficial effects of melatonin on stroke-induced muscle atrophy in focal cerebral ischemic rats

“…In a previous study, we confirmed that a controlled photoperiod could change plasma levels of melatonin [26]. Moreover, therapeutic effect of melatonin could modulate via both photoperiod control and exogenous melatonin administration on reconstruction of neural network after spinal cord injury in rats [20]. In clinical trials, likewise, melatonin administration (10 mg/day) induces reduction of progression of non-alcoholic fatty liver disease through improves plasma liver enzymes [27].…”

“…In a previous study, we demonstrated that exogenous and endogenous melatonin has a prophylactic effect on muscle atrophy in the hindlimb in spinal cord-injured rats [20]. In vivo studies have shown that melatonin treatment increases the expression of IGF-1 in a castration animal model [21].…”

Melatonin as an Interventional Novel Candidate for the Individual with Autistic Fragile X Syndrome in Human

“…Recently, melatonin has been reported that could act as neuroprotective agent against neurological injury [104][105][106][107]. In experimental study, rodents injected with melatonin plus dexamethasone that has a neurotoxic action on hippocampus has been demonstrated the neuroprotective effect of melatonin.…”

Melatonin as a Novel Interventional Candidate for Fragile X Syndrome with Autism Spectrum Disorder in Humans

“…Recently, it was reported that melatonin acts as a neuroprotective agent against neurological injuries [111,112,113,114]. The neuroprotective effects of melatonin have been demonstrated by in vivo studies that co-administered injections of melatonin and dexamethasone, the latter of which is known to be neurotoxic to cells in the hippocampus.…”