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

Authors

  • Jie Fu,

    1. Key Laboratory of the Ministry of Education for Experimental Teratology, Department of Histology and Embryology, Shandong University School of Medicine, Jinan, Shandong, China
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    • These two authors contributed equally to the study.

  • Shi-Dou Zhao,

    1. Key Laboratory of the Ministry of Education for Experimental Teratology, Department of Histology and Embryology, Shandong University School of Medicine, Jinan, Shandong, China
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    • These two authors contributed equally to the study.

  • Hui-Juan Liu,

    1. Bio-X Center, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, China
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  • Qiu-Huan Yuan,

    1. Key Laboratory of the Ministry of Education for Experimental Teratology, Department of Histology and Embryology, Shandong University School of Medicine, Jinan, Shandong, China
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  • Shang-Ming Liu,

    1. Key Laboratory of the Ministry of Education for Experimental Teratology, Department of Histology and Embryology, Shandong University School of Medicine, Jinan, Shandong, China
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  • Yan-Min Zhang,

    1. Key Laboratory of the Ministry of Education for Experimental Teratology, Department of Histology and Embryology, Shandong University School of Medicine, Jinan, Shandong, China
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  • Eng-Ang Ling,

    1. Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Republic of Singapore
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  • Ai-Jun Hao

    1. Key Laboratory of the Ministry of Education for Experimental Teratology, Department of Histology and Embryology, Shandong University School of Medicine, Jinan, Shandong, China
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Address reprint requests to Ai-Jun Hao, Key Laboratory of the Ministry of Education for Experimental Teratology, Department of Histology and Embryology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong 250012, China.
E-mail: aijunhao@sdu.edu.cn

Abstract

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.

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