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首页> 外文学位 >Melatonin Potentiates Running Induced Neurogenesis in the Dentate Gyrus of Adult C3H/HeN mice.
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Melatonin Potentiates Running Induced Neurogenesis in the Dentate Gyrus of Adult C3H/HeN mice.

机译：褪黑素增强了成年C3H / HeN小鼠齿状回中奔跑诱导的神经发生。

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摘要

Impairment of hippocampus neurogenesis has been associated with neurodegenerative and psychiatric disorders such as Alzheimer's disease and major depression. By studying mechanisms regulating the distinct phases of neurogenesis, including proliferation of progenitor cells, selective survival, and functional integration of new neurons, we can gain insight into the pathology and treatment of these disorders. In laboratory rodents, environmental enrichments, e.g. running wheel (RW) activity can stimulate adult neurogenesis in the dentate gyrus (van Praag, et al. 1999). The pineal hormone melatonin, via activation of the MT1 and MT2 G-protein coupled receptors modulates sleep and circadian rhythms which are altered in major depression (Dubocovich et al., 2005). It has been reported that melatonin enhances neurogenesis by modulating cell survival (Ramirez-Rodiguez et al., 2009). Therefore we hypothesized that melatonin can potentiate neurogenesis induced by RW activity in adult mice.;To assess the role of melatonin treatment on RW induced cell proliferation and survival, single housed C3H/HeN mice (3--4 month old) in a 12/12 hr light/dark cycle with access to fixed wheels (FW) or RW were treated with vehicle (VEH: 0.01% ethanol) or melatonin: (0.02 mg/ml in VEH) via drinking water ad libitum for 12 days. Six injections of bromodeoxyuridine (BrdU 75mg/kg, ip) were given at 12 hr intervals started on day 9. Brains were collected on day 12 to assess alterations in cell proliferation or on day 40 to determine cell survival. In the survival group, wheel activity was continued after the 12 days but treatments were removed. One in six hippocampal coronal sections (50 um) collected for immunohistochemistry. Cell proliferation and survival were quantified by determining the number of BrdU-labeled cells in the inner granular cell layer across six sections of dentate gyrus. RW activity increased cell proliferation by 65.9% (p0.0001 by two way ANOVA). Melatonin treatment did not affect cell proliferation in the FW and RW groups. RW activity increased cell survival by 210% (p0.0001 by two way ANOVA). Melatonin treatment did not affect cell survival in the FW group but increased the RW induced cell survival by 47.3% compared to VEH treatment (p0.05 Bonferroni posttests). The phenotype of surviving neuron is confirmed by BrdU and NeuN colocalization. Our data indicate a role for melatonin in increasing the survival of new hippocampal neuron whose formation is induced by RW activity. This capacity of melatonin is selective for the survival phase of neurogenesis because no effect was observed in the cell proliferation phase. We conclude that melatonin increases RW induced neurogenesis by increasing cell survival without modulating cell proliferation in the dentate gyrus. This positive response to melatonin requires RW activity suggesting a novel role of melatonin regulating neurogenesis.
机译：海马神经发生受损与神经退行性疾病和精神疾病有关，例如阿尔茨海默氏病和严重抑郁症。通过研究调节神经发生不同阶段的机制，包括祖细胞增殖，选择性存活和新神经元的功能整合，我们可以深入了解这些疾病的病理和治疗方法。在实验室啮齿动物中，环境富集，例如运转轮（RW）的活动可以刺激齿状回中的成年神经发生（van Praag等，1999）。松果体褪黑激素通过激活MT1和MT2 G蛋白偶联受体来调节睡眠和昼夜节律，这在重度抑郁症中有所改变（Dubocovich等，2005）。据报道，褪黑激素通过调节细胞存活来增强神经发生（Ramirez-Rodiguez et al。，2009）。因此，我们假设褪黑激素可以增强成年小鼠RW活性诱导的神经发生。;为了评估褪黑激素治疗对RW诱导的细胞增殖和存活的作用，在12 /通过车辆（VEH：0.01％乙醇）或褪黑激素：（VEH中为0.02 mg / ml）随意饮水处理12小时的明/暗循环并进入固定车轮（FW）或RW。从第9天开始以12小时间隔注射六次溴脱氧尿苷（BrdU 75mg / kg，ip）。在第12天收集大脑以评估细胞增殖的改变，或在第40天收集大脑以确定细胞存活率。在存活组中，在12天后车轮活动继续进行，但取消了治疗。收集六分之一的海马冠状切片（50 um）用于免疫组化。通过确定横跨齿状回的六个部分的内部颗粒细胞层中BrdU标记的细胞的数量来量化细胞增殖和存活。 RW活性使细胞增殖提高了65.9％（通过两种方差分析，p <0.0001）。褪黑素处理在FW和RW组中不影响细胞增殖。 RW活性使细胞存活率提高了210％（通过两种方差分析，p <0.0001）。褪黑素治疗不影响FW组的细胞存活，但与VEH治疗相比，RW诱导的细胞存活增加了47.3％（p <0.05 Bonferroni后测）。存活神经元的表型通过BrdU和NeuN共定位来确认。我们的数据表明褪黑激素在增加新海马神经元存活中的作用，新海马神经元的形成是由RW活性诱导的。褪黑激素的这种能力对于神经发生的存活阶段具有选择性，因为在细胞增殖阶段未观察到作用。我们得出的结论是，褪黑激素通过增加细胞存活而不调节齿状回中的细胞增殖来增加RW诱导的神经发生。对褪黑激素的这种阳性反应需要RW活性，提示褪黑激素调节神经发生的新作用。

著录项

  • 作者

    Liu, Jiabei JJ.;

  • 作者单位

    State University of New York at Buffalo.;

  • 授予单位 State University of New York at Buffalo.;
  • 学科 Biology Neuroscience.;Health Sciences Pharmacology.
  • 学位 M.S.
  • 年度 2011
  • 页码 67 p.
  • 总页数 67
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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