MELATONIN: NEURITOGENESIS & NEUROPROTECTIVE EFFECTS IN CRUSTACEAN X-ORGAN CELLS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 褪黑素是一种脊椎动物激素，在各种代谢过程的昼夜节律中扮演着许多角色。最近对大鼠神经母细胞瘤细胞的研究表明，褪黑素既具有神经生成作用，又具有神经保护作用。先前的研究表明，褪黑素在甲壳动物生理学中可能具有系统发育保守的作用。我们正在研究一种甲壳类细胞亚型，即X器官细胞，这种细胞是多极的，在培养中显示出快速的轴突生长和树枝状生长。与研究充分的神经母细胞瘤细胞不同，甲壳类细胞是高度分化的，是神经分泌细胞；它们类似于脊椎动物下丘脑神经分泌细胞。这些细胞的生长模式和活动，以及它们易于培养，为褪黑素在各种细胞活动中的作用提供了一个模型系统。我们目前的研究表明，褪黑素以剂量依赖和潜在的受体介导的方式促进这些细胞中的轴突生长。此外，褪黑素在细胞暴露在生长抑制但不致命的过氧化氢水平时起到保护作用。免疫细胞化学显示褪黑素受体样结合在这些细胞上，我实验室以前的工作表明褪黑素可能诱导这些细胞释放神经肽。我们目前正在研究这些受体，并正在探索褪黑素对x器官细胞的神经分泌和神经发生活动的细胞和分子效应。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Melatonin is a vertebrate hormone that plays numerous roles in circadian timing of a variety of metabolic processes. Recent studies in rat neuroblastoma cells show both a neuritogenic and a neuroprotective influence of melatonin. Previous studies have shown that melatonin may have phylogenetically-conserved roles in crustacean physiology. We are studying a crustacean cell subtype, the x-organ cell, that is multipolar and shows rapid neurite outgrowth and arborization in culture. Unlike the well-studied neuroblastoma cells, crustacean cells are highly differentiated and are neurosecretory; they are analogous to vertebrate hypothalamic neurosecretory cells. The growth patterns and activities of these cells, and their ease of culture, provide a model system for the roles of melatonin in a variety of cell activities. Our current studies have shown that melatonin enhances neurite growth in these cells in a dose-dependent and potentially receptor-mediated manner. Furthermore, melatonin plays a protective role in response to exposure of the cells to growth-inhibiting but nonlethal levels of hydrogen peroxide. Immunocytochemistry indicates melatonin receptor-like binding on these cells, and prior work in my laboratory has shown that melatonin likely induces the release of neuropeptides from these cells. We are currently studying these receptors and are exploring the cellular and molecular effects of melatonin on the neurosecretory and neuritogenic activities of x-organ cells.