Melatonin Modulates Cell Survival of New Neurons in the Hippocampus of Adult Mice
Melatonin Modulates Cell Survival of New Neurons in the Hippocampus of Adult Mice
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DOI：
10.1038/npp.2009.46
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发表时间：
2009-08-01
影响因子：
7.6
通讯作者：
Kempermann, Gerd
中科院分区：
文献类型：
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作者：
Ramirez-Rodriguez, Gerardo;Klempin, Friederike;Kempermann, Gerd
成人海马神经发生的调节受昼夜节律的影响，受睡眠操纵的影响，并在情感障碍的动物模型中受到干扰。这些观察结果以及褪黑激素昼夜节律产生失调与神经精神疾病之间的联系促使我们研究褪黑激素在控制成人海马神经发生中的潜在作用。在体外实验中，褪黑素通过促进细胞存活，增加了体外成人海马神经前体细胞衍生的新神经元数量。这种作用部分依赖于褪黑激素受体的激活，因为它可以被受体拮抗剂卢津多阻断。褪黑素对细胞增殖无影响。同样，在体内成年C57BL/6小鼠齿状回中，外源性褪黑素（8 mg/kg）也能提高神经元祖细胞和有丝分裂后未成熟神经元的存活率。褪黑素不影响体内前体细胞增殖，也不影响神经元和神经胶质细胞的成熟。此外，褪黑素在Porsolt强迫游泳试验中显示出类似抗抑郁的作用。这些结果表明，褪黑素可以通过其受体调节成年海马新生神经元的存活，使其成为已知的第一个具有这种特异性的外源性适用物质神经精神药理学（2009）34,2180-2191；doi: 10.1038 / npp.2009.46;2009年5月6日在线发布
Regulation of adult hippocampal neurogenesis is influenced by circadian rhythm, affected by the manipulation of sleep, and is disturbed in animal models of affective disorders. These observations and the link between dysregulation of the circadian production of melatonin and neuropsychiatric disorders prompted us to investigate the potential role of melatonin in controlling adult hippocampal neurogenesis. In vitro, melatonin increased the number of new neurons derived from adult hippocampal neural precursor cells in vitro by promoting cell survival. This effect was partially dependent on the activation of melatonin receptors as it could be blocked by the application of receptor antagonist luzindole. There was no effect of melatonin on cell proliferation. Similarly, in the dentate gyrus of adult C57BL/6 mice in vivo, exogenous melatonin (8 mg/kg) also increased the survival of neuronal progenitor cells and post-mitotic immature neurons. Melatonin did not affect precursor cell proliferation in vivo and also did not influence neuronal and glial cell maturation. Moreover, melatonin showed antidepressant-like effects in the Porsolt forced swim test. These results indicate that melatonin through its receptor can modulate the survival of newborn neurons in the adult hippocampus, making it the first known exogenously applicable substance with such specificity Neuropsychopharmacology (2009) 34, 2180-2191; doi:10.1038/npp.2009.46; published online 6 May 2009