Melatonin promotes proliferation and differentiation of neural stem cells subjected to hypoxia in vitro

Abstract

Melatonin, an endogenously produced neurohormone secreted by the pineal gland, has a variety of physiological functions and neuroprotective effects. It can modulate the functions of neural stem cells (NSCs) including proliferation and differentiation in embryonic brain tissue but its effect and mechanism on the stem cells in hypoxia remains to be explored. Here, we show that melatonin stimulates proliferation of NSCs during hypoxia. Additionally, it also promoted the differentiation of NSCs into neurons. However, it did not appear to exert an obvious effect on the differentiation of astrocytes. The present results have further shown that the promotional effect of NSCs proliferation by melatonin involved the MT1 receptor and increased phosphorylation of ERK1/2. The effect of melatonin on differentiation of NSCs is linked to altered expression of differentiation-related genes. In the light of these findings, it is suggested that melatonin may be beneficial as a supplement for treatment of neonatal hypoxic-ischemic brain injury for promoting the proliferation and differentiation of NSCs.

Melatonin promotes goat spermatogonia stem cells (SSCs) proliferation by stimulating glial cell line-derived neurotrophic factor (GDNF) production in Sertoli cells

“…In human adult MSCs, for instance, melatonin combined with the extracellular matrix can enhance cellular alkaline phosphatase (AP) activity, induce osteogenesis via the melatonin receptor 2 (MT2), and also reverse stress-induced MSC injuries [10–13]. Meanwhile, melatonin can elevate the viability of rat neural stem cells (NSCs) and induce NSCs differentiate into dopaminergic neurons and decrease astrocyte production [14, 15]. Interestingly, some studies have shown that melatonin can increase the production of Brain-Derived Neurotrophic Factor (BDNF) and glial cell-derived neurotrophic factor (GDNF) in cultured NSCs, both of which are integral to neuronal development and differentiation [16].…”

Beneficial Effects of Melatonin Combined with Exercise on Endogenous Neural Stem/Progenitor Cells Proliferation after Spinal Cord Injury

“…In addition to physiological roles of melatonin, such as in circadian regulation, recent studies have shown that melatonin can enhance adult stem cell viability, proliferation, and differentiation, including that of mesenchymal stem cells into osteoblasts [18,19] and eNSPCs into neurons [20–23], suggesting the application of melatonin in regulating neurogenesis of eNSPCs in the central nervous system, including the spinal cord. Additionally, melatonin stimulates proliferation of eNSPCs and promotes neuronal differentiation under hypoxic condition in vitro [24]. However, to date, there has been no reported study evaluating melatonin treatment of eNSPCs after SCI.…”

Melatonin Attenuates Histopathological Changes in the Hippocampus of Infantile Rats with Kaolin-Induced Hydrocephalus

“…It also has anti-oxidative, anti-inflammatory, free radical scavenger, anti-aging, and neuroprotective effects, which have been connected with the redox status of cells and tissues, thus suggesting its potential clinical role in various neurodegenerative diseases [22-24, 43]. Recently, it has been proposed that melatonin promotes irradiation-induced inhibition of neurogenesis [29, 44] and proliferation, and differentiation of neural stem cells during hypoxia [45]. Accordingly, our findings also confirm that melatonin attenuates histopathological changes in the hippocampus of infantile rats with kaolin-induced chronic hydrocephalus.…”