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首页> 外文学位 >Hypocretin, neuronal activity-regulated pentraxin and melanin-concentrating hormone: Relevance to narcolepsy.
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Hypocretin, neuronal activity-regulated pentraxin and melanin-concentrating hormone: Relevance to narcolepsy.

机译：降钙素，神经元活动调节的五环素和黑色素浓缩激素：与发作性睡病的相关性。

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摘要

Hypocretin (Hcrt) is a neuropeptide synthesized in the hypothalamus. Cells containing Hcrt also contain neuronal activity-regulated pentraxin (Narp), a pentraxin involved in the clustering of AMPA receptors. Hcrt/Narp positive cells are located in close proximity to cells containing melanin-concentrating hormone (MCH), and evidence suggests that these two cell groups interact. Narcolepsy is a sleep disorder characterized by sleep attacks and cataplexy triggered by emotion and has been linked to a near complete loss of Hcrt staining, although MCH staining remains unaltered. It is not known whether the loss of Hcrt staining represents the specific loss of the peptide Hcrt or actual loss of the Hcrt-synthesizing cells. We employed immunocytochemistry in post-mortem narcoleptic brains to show that Narp staining is also decreased in the human narcoleptic hypothalamus to the same extent that Hcrt staining is lost. These findings indicate that either both Hcrt and Narp synthesis is lost in narcolepsy or, more likely, that the cells containing both Hcrt and Narp are lost. Because Hcrt cells normally interact with MCH and because the Hcrt cells appear to be lost in narcolepsy, it is unclear how this may affect the MCH system and what functional implications this may have for narcolepsy. Therefore, using microdialysis, we measured Hcrt and MCH release in the non-narcoleptic human brain and in the rat brain to assess the pattern of release of these two peptides during sleep and waking behavior. We found that Hcrt and MCH exhibit an opposite release pattern. Hcrt levels increase at wake onset and are high during wake, while MCH levels increase at sleep onset and are high during sleep. Furthermore, Hcrt levels are high during social interaction and during emotional situations, while MCH levels are low. Because Hcrt and MCH cells likely interact with each other and because they show opposite patterns of release, it is likely that these two systems oppose each other functionally. Thus, without the Hcrt cells, narcoleptics may experience a dysregulation of the MCH system, increases of MCH at inappropriate times such as during emotional and social situations, and invasion of their waking state by components of sleep.
机译：降钙素（Hcrt）是在下丘脑中合成的神经肽。含有Hcrt的细胞还含有神经元活性调节的五聚毒素（Narp），这是一种参与AMPA受体聚集的五聚毒素。 Hcrt / Narp阳性细胞紧邻含有黑色素浓缩激素（MCH）的细胞，证据表明这两个细胞群相互作用。发作性睡病是一种睡眠障碍，其特征是情绪引发的睡眠攻击和中枢性瘫痪，尽管MCH染色保持不变，但与Hcrt染色几乎完全丧失有关。尚不清楚Hcrt染色的缺失代表肽Hcrt的特异性缺失还是Hcrt合成细胞的实际缺失。我们在死后的麻醉性大脑中进行了免疫细胞化学研究，以显示人麻醉性下丘脑中的Narp染色也减少到与Hcrt染色消失相同的程度。这些发现表明，Hcrt和Narp的合成在发作性睡病中都丢失了，或更可能是同时含有Hcrt和Narp的细胞也丢失了。由于Hcrt细胞通常会与MCH相互作用，并且由于Hcrt细胞在发作性睡病中似乎会丢失，因此尚不清楚这可能如何影响MCH系统以及这对发作性睡病有何功能意义。因此，使用微透析，我们测量了非麻醉性人脑和大鼠脑中的Hcrt和MCH释放，以评估在睡眠和苏醒行为中这两种肽的释放模式。我们发现Hcrt和MCH表现出相反的释放模式。 Hcrt水平在醒来时增加，在醒来时较高，而MCH水平在睡眠时增加，在睡眠时很高。此外，在社交互动和情绪状况下，Hcrt水平较高，而MCH水平较低。由于Hcrt细胞和MCH细胞可能彼此相互作用，并且由于它们显示出相反的释放模式，因此这两个系统在功能上可能彼此相对。因此，在没有Hcrt细胞的情况下，止痛药可能会经历MCH系统失调，在不适当的时间（例如在情绪和社交环境中）MCH升高，以及睡眠中的清醒状态入侵。

著录项

  • 作者

    Blouin, Ashley Marie.;

  • 作者单位

    University of California, Los Angeles.;

  • 授予单位 University of California, Los Angeles.;
  • 学科 Biology Neuroscience.
  • 学位 Ph.D.
  • 年度 2009
  • 页码 107 p.
  • 总页数 107
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

  • 入库时间 2022-08-17 11:38:19

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