RESUMEN
Diabetes mellitus (DM) is a multisystem endocrine disorder affecting the brain. Mesenchymal stem cells (MSCs) pretreated with Melatonin have been shown to increase the potency of MSCs. This work aimed to compare Melatonin, stem cells, and stem cells pretreated with Melatonin on the cognitive functions and markers of synaptic plasticity in an animal model of type I diabetes mellitus (TIDM). Thirty-six rats represented the animal model; six rats for isolation of MSCs and 30 rats were divided into five groups: control, TIDM, TIDM + Melatonin, TIDM + Stem cells, and TIDM + Stem ex vivo Melatonin. Functional assessment was performed with Y-maze, forced swimming test and novel object recognition. Histological and biochemical evaluation of hippocampal Neuroligin 1, Sortilin, Brain-Derived Neurotrophic Factor (BDNF), inducible nitric oxide synthase (iNOS), toll-like receptor 2 (TLR2), Tumor necrosis factor-alpha (TNF-α), and Growth Associated Protein 43 (GAP43). The TIDM group showed a significant decrease of hippocampal Neuroligin, Sortilin, and BDNF and a significant increase in iNOS, TNF-α, TLR2, and GAP43. Melatonin or stem cells groups showed improvement compared to the diabetic group but not compared to the control group. TIDM + Stem ex vivo Melatonin group showed a significant improvement, and some values were restored to normal. Ex vivo melatonin-treated stem cells had improved spatial working and object recognition memory and depression, with positive effects on glucose homeostasis, inflammatory markers levels and synaptic plasticity markers expression.
RESUMEN
Peripheral nerve injuries can cause disabilities, social or economic problems. Melatonin, the secretory product of the pineal gland has antioxidant and anti-inflammatory actions. The aim of the present study was to investigate the effect of melatonin on the recovery of sciatic nerve after injury, comparing its effect when given in the light or the dark periods. Forty adult male Albino rats were allocated into four groups: control, nerve injury, nerve injury + melatonin given at light and nerve injury + melatonin given at dark. Nerve injury was initiated by clamping the sciatic nerve. Sciatic functional index (SFI) was measured preoperatively and postoperatively. Melatonin was given daily for six weeks. Recovery of the function was analyzed by functional analysis, electrophysiological analysis and biochemical measurement of Superoxide dismutase (SOD), Interleukin 1-beta (IL-1 ß), Nerve growth factor (NGF), and bcl-2. Melatonin improved SFI, nerve conduction velocity (NCV) and the force of gastrocnemius muscle contraction as compared to the untreated rats. SOD activity, NGF, and bcl-2 were significantly increased, while IL-1ß was significantly decreased after melatonin treatment as compared to the untreated injury group. SFI reached the control level; muscle contraction and IL-1B were significantly improved in the group treated with melatonin in the dark. Melatonin fastened the neural recovery and may be used in the treatment of nerve injury and it induced better nerve regeneration when the rats were treated during the dark period.