Melatonin influences the proliferative and differentiative activity of neural stem cells
Melatonin influences the proliferative and differentiative activity of neural stem cells
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DOI：
10.1111/j.1600-079x.2007.00435.x
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发表时间：
2007-04-01
影响因子：
10.3
通讯作者：
Shinohara, Kazuyuki
中科院分区：
文献类型：
--
作者：
Moriya, Takahiro;Horie, Nobutaka;Shinohara, Kazuyuki
褪黑素具有多种生物学功能，但其对神经干细胞的影响尚不清楚。在这项研究中，我们在体外培养系统中检测了生理浓度（0.01-10 nM）或药理学浓度（1-100 μ M）褪黑素对小鼠胚胎纹状体中NSCs的增殖和神经和星形胶质细胞分化的影响。我们发现，褪黑激素在药理学浓度下，而不是在生理浓度下，以浓度依赖的方式抑制表皮生长因子（EGF）刺激的NSC增殖（活细胞的增加，DNA合成和神经球形成）。此外，在增殖期间使用药理学浓度的褪黑激素，促进了1% fbs诱导的NSCs神经分化，而不影响星形胶质细胞的分化。相反，在分化期间用药理学浓度的褪黑激素治疗会降低NSCs的神经分化。与褪黑激素一样，MCI-186（一种抗氧化剂）抑制egf刺激的NSC增殖，并促进NSCs随后的神经分化。这些结果表明，褪黑素可能通过其抗氧化活性对NSC功能发挥强大的调节作用，包括抑制增殖和促进神经元分化。由于神经发生被认为在改善神经退行性疾病的缺陷中起重要作用，褪黑素可能有益于脑梗死等疾病的治疗。
Though melatonin has a wide variety of biological functions, its effects on the neural stem cells (NSCs) is still unknown. In this study, we examined the effects of melatonin at either physiological (0.01-10 nM) or pharmacological concentrations (1-100 mu M) on the proliferation and neural and astroglial differentiation of NSCs derived from the mouse embryo striatum using an in vitro culture system. We found that melatonin at pharmacological concentrations, but not at physiological concentrations, suppressed epidermal growth factor (EGF)-stimulated NSC proliferation (increment of viable cells, DNA synthesis and neurosphere formation) in a concentration-dependent manner. Furthermore, treatment with melatonin at a pharmacological concentration during the proliferation period facilitated 1% FBS-induced neural differentiation of NSCs without affecting the astroglial differentiation. In contrast, the treatment with melatonin at pharmacological concentrations during the differentiation period decreased the neural differentiation of the NSCs. As with melatonin, MCI-186, an antioxidant, suppressed EGF-stimulated NSC proliferation and facilitated the subsequent neural differentiation of NSCs. These results suggest that melatonin exerts potent modulatory effects on NSC functions including the suppression of the proliferation and facilitation of neuronal differentiation, likely via its antioxidant activity. As neurogenesis is thought to play an important role in ameliorating the deficit in neurodegenerative diseases, melatonin might be beneficially used for the treatment diseases such as cerebral infarction.