中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2019, Vol. 14 ›› Issue (10): 1787-1795.doi: 10.4103/1673-5374.257537

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

褪黑素促进长期睡眠剥夺条件下成年小鼠海马齿状回中神经祖细胞增殖

  

  • 出版日期:2019-10-15 发布日期:2019-10-15
  • 基金资助:

    这项研究得到了瓜达拉哈拉大学（PROSNI 2016,2017-8）提供的资助，部分资金来自Consejo Nacional de Ciencia y Tecnologia（CONACyT No. PN 2016-01-465和INFR-280414）和PRODEP（213544），以及CONGyT奖学金（374823）

Melatonin modifies SOX2+ cell proliferation in dentate gyrus and modulates SIRT1 and MECP2 in long-term sleep deprivation

Alan Hinojosa-Godínez 1, Luis F. Jave-Suarez 3, Mario Flores-Soto 4, Alma Y. Gálvez-Contreras 1, 6, Sonia Luquín 1, Edith Oregon-Romero 5, Oscar González-Pérez 2, Rocio E. González-Castañeda 1, 6   

  1. 1 Laboratorio de Microscopía de Alta Resolución, Departamento de Neurociencias, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, México
    2 Laboratorio de Neurociencias, Facultad de Psicología, Universidad de Colima, Colima, México
    3 División de Inmunología, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Guadalajara, México
    4 División de Neurociencias, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Guadalajara, México
    5 Instituto de Investigación en Ciencias Biomédicas (IICB), Departamento de Biología Molecular y Genómica, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, México
    6 Unidad de Atención en Neurociencias, Departamento de Neurociencias. Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, México
  • Online:2019-10-15 Published:2019-10-15
  • Contact: Rocio E. González-Casta?eda, PhD, rocio.gcastaneda@academicos.udg.mx.
  • Supported by:

    This work was supported by grants from Universidad de Guadalajara (PROSNI 2016, 2017-8) to REGC and partially by grants from Consejo Nacional de Ciencia y Tecnologia (CONACyT No. PN 2016-01-465 and INFR-280414) and PRODEP (213544) to OGP, and the CONACyT Fellowship grant (374823) to AHG

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摘要：

研究已显示，褪黑激素可促进短期睡眠剥夺后成年海马神经干细胞的增殖；然而，其在长期睡眠剥夺中对神经干细胞调节机制尚未见报道。为此，实验拟观察褪黑素干预对96h睡眠剥夺小鼠海马神经干细胞增殖的影响，并通过计算文本挖掘和关键词聚类预测和定量PCR分析表观遗传标志物的表达，以免疫印迹法检测表观遗传调节因子甲基-CpG-结合蛋白2和去乙酰化酶1的表达，以免疫荧光染色检测神经干细胞增殖情况。结果显示，褪黑激素增加了睡眠剥夺小鼠海马表观遗传标志物Let-7b，mir-132和mir-124的表达，上调了表观遗传调节因子MECP2和SIRT1的表达，并使睡眠剥夺小鼠海马齿状回神经干细胞标志物Sox2+和细胞增殖标志物BrdU+的双标阳性细胞数量增加。从而说明褪黑素通过改变表观遗传调节因子的表达，促进长期睡眠剥夺的条件下成年海马齿状回中神经祖细胞的增殖。研究于2016年1月2日获得墨西哥瓜达拉哈拉大学动物伦理委员会批准（CI-16610）。

orcid: 0000-0001-6220-5456 (Rocio E. González-Castañeda)

关键词: 睡眠剥夺, 褪黑激素, microRNA, 神经发生, Sirtuin 1, SIRT1, 甲基-CpG结合蛋白2, MECP2, 表观遗传, 文本挖掘, mir-9, let-7b

Abstract:

Melatonin is a pleiotropic molecule that, after a short-term sleep deprivation, promotes the proliferation of neural stem cells in the adult hippocampus. However, this effect has not been observed in long-term sleep deprivation. The precise mechanism exerted by melatonin on the modulation of neural stem cells is not entirely elucidated, but evidence indicates that epigenetic regulators may be involved in this process. In this study, we investigated the effect of melatonin treatment during a 96-hour sleep deprivation and analyzed the expression of epigenetic modulators predicted by computational text mining and keyword clusterization. Our results showed that the administration of melatonin under sleep-deprived conditions increased the MECP2 expression and reduced the SIRT1 expression in the dentate gyrus. We observed that let-7b, mir-132, and mir-124 were highly expressed in the dentate gyrus after melatonin administration, but they were not modified by sleep deprivation. In addition, we found more Sox2+/5-bromo-2′-deoxyuridine (BrdU)+ cells in the subgranular zone of the sleep-deprived group treated with melatonin than in the untreated group. These findings may support the notion that melatonin modifies the expression of epigenetic mediators that, in turn, regulate the proliferation of neural progenitor cells in the adult dentate gyrus under long-term sleep-deprived conditions. All procedures performed in this study were approved by the Animal Ethics Committee of the University of Guadalajara, Mexico (approval No. CI-16610) on January 2, 2016.

Key words: sleep-deprivation, melatonin, microRNA, neurogenesis, Sirtuin 1, SIRT1, methyl-CpG-binding protein 2, MECP2, epigenetic, text-mining, mir-9, let-7b