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首页> 外文学位 >Microglial purinergic receptor regulation by physiological factors and role in TNFalpha production.
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Microglial purinergic receptor regulation by physiological factors and role in TNFalpha production.

机译：小胶质嘌呤能受体受生理因素的调节及其在TNFα产生中的作用。

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摘要

As the primary resident immune cell population in the CNS, microglia react to injury or infection and produce immunomodulatory factors. Uncontrolled microglial activation is thought to contribute to the pathology of several neurodegenerative disorders, many with incidence rates that vary by age and sex. Purinergic receptors (P2Rs) have been shown to modulate microglial activity, however prior to this study, alterations in P2R expression as a result of sex or aging had not been investigated. The expression of the rodent P2Rs and select associated genes was examined in microglia freshly-isolated from mice ranging in age from three days to 12 months-old. Many P2Rs showed increased expression in older mice, and the expression of some was sexually dimorphic at certain ages. Similarly, basal expression of many proinflammatory and neuroprotective genes in microglia was highest in adult mice. It was also observed that culturing microglia dramatically alters gene expression: ten P2Rs were affected; four changed by 90-fold or greater.;Neuronal populations vary across the CNS, but it was unknown if different local environments also resulted in microglial heterogeneity. Microglia isolated from five different CNS regions displayed differences in the expression of P2Rs and other genes. Levels were often lowest in spinal cord microglia, while the inverse was observed for TNFalpha. The pattern of microglial gene expression across the CNS sometimes changed with animal age or differed between males and females.;The presence of sexual dimorphisms in microglial gene expression suggests regulation by gonadal hormones. Treatment of mice with estrogen altered microglial expression of several P2Rs, often in a manner that was sex-dependent or influenced by gonadectomy. In addition, P2R activation with ADP resulted in decreased expression and release of TNFalpha from LPS-treated microglia in a manner consistent with P2Y13 signaling - the first identified function of this receptor in microglia.;The novel research presented here addresses unexplored areas necessary for a more complete understanding of microglial biology, and will form the foundation for future studies examining microglial contributions to normal and pathological CNS function.
机译：小胶质细胞是中枢神经系统的主要固有免疫细胞群，对损伤或感染有反应并产生免疫调节因子。人们认为，不受控制的小胶质细胞活化可导致多种神经退行性疾病的病理，许多疾病的发生率随年龄和性别而变化。嘌呤能受体（P2Rs）已被证明可调节小胶质细胞的活性，但在此研究之前，尚未研究过性别或衰老导致P2R表达的改变。在从三天到十二个月大的小鼠新鲜分离的小胶质细胞中检查了啮齿动物P2Rs和选择的相关基因的表达。许多P2R在老年小鼠中表现出增加的表达，并且某些表达在某些年龄是性二态的。同样，成年小鼠中小胶质细胞中许多促炎和神经保护基因的基础表达最高。还观察到，培养小胶质细胞会显着改变基因表达：十个P2R受到影响。四个改变了90倍或更多。；整个CNS的神经元数量各不相同，但尚不清楚不同的当地环境是否也会导致小胶质细胞异质性。从五个不同的CNS区域中分离出的小胶质细胞在P2Rs和其他基因的表达上存在差异。脊髓小胶质细胞中的水平通常最低，而TNFα则相反。整个中枢神经系统中小胶质细胞基因表达的模式有时会随着动物年龄的变化而变化，或者在雄性和雌性之间有所不同。；小胶质细胞基因表达中存在性二态性提示性腺激素对其进行调节。用雌激素治疗小鼠通常以性别依赖性或受性腺切除术影响的方式改变了几种P2R的小胶质细胞表达。此外，ADP对P2R的激活导致LLP处理的小胶质细胞的TNFalpha的表达和释放减少，与P2Y13信号传导一致-这是该受体在小胶质细胞中的第一个功能。对小胶质细胞生物学有更全面的了解，并将为将来研究小胶质细胞对正常和病理中枢神经系统功能的贡献奠定基础。

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  • 作者

    Crain, Jessica Morgan.;

  • 作者单位

    The University of Wisconsin - Madison.;

  • 授予单位 The University of Wisconsin - Madison.;
  • 学科 Biology Neuroscience.;Health Sciences Immunology.
  • 学位 Ph.D.
  • 年度 2009
  • 页码 221 p.
  • 总页数 221
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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