Production and Glia-Axon Transfer of Heat Shock and Other Glial Proteins

当神经胶质细胞存在时，神经元的功能会更好，但由于很难将神经胶质分子与轴突分子分离，导致这种效果的神经胶质分子所知甚少。然而，这种分离可以在鱿鱼巨型轴突中实现，因为它的大小（通常长3-6厘米，直径0.5毫米）。最近，本研究者发现转移到鱿鱼轴突的胶质蛋白中有一种属于热应激蛋白。大多数细胞在急性暴露于代谢应激后会大量产生这些蛋白质。随着蛋白质的积累，细胞对潜在的致命压力变得更有抵抗力。神经胶质-轴突传递应激蛋白的发现代表了对神经系统损伤反应的理解的一个潜在突破，因为它意味着神经胶质可以向轴突提供旨在防止轴突在面对创伤时死亡的蛋白质。在鱿鱼巨轴突中，将采用生化、免疫化学和形态学技术来研究应激蛋白的合成和胶质-轴突转移与轴突耐受性之间的关系。此外，将应激蛋白的转移与其他胶质蛋白的转移进行比较，以确定是否存在胶质-轴突蛋白转移的多种机制。在这个研究项目中描述的工作将展示如何在神经组织中增强应激蛋白反应。这些信息可能提供一种工具，可以帮助改善中枢神经系统损伤后的功能丧失。潜在地，神经系统创伤后的恢复可以通过刺激应激蛋白的产生或通过管理应激蛋白来改善。更为深远的可能性是，神经系统物理创伤后神经元的损失可以通过适当操纵应激蛋白反应来减少。

Neurons function better in the presence of glial cells, but few of the glial molecules responsible for that effect are known because of the difficulty in separating them from axonal molecules. However, that separation can be achieved in the squid giant axon because of its size (typically 3-6 cm long and 0.5 mm in diameter). Recently, this investigator found that one of the glial proteins transferred into the squid axon belongs to the group of heat stress proteins. These proteins are produced in abundance by most cells after acute exposure to metabolic stress. As the proteins accumulate, the cells become more resistant to potentially lethal stress. The discovery of glia-axon transfer of stress proteins represents a potential breakthrough in the understanding of nervous system response to injury because it implies that the glia can provide to the axon proteins designed to keep the axon from dying in the face of trauma. In the squid giant axon, biochemical, immunochemical and morphological techniques will be used to examine the relationship between the synthesis and glia-axon transfer of stress proteins and axonal stress tolerance. Additionally, stress proteins transfer will be compared to the transfer of other glial proteins to determine if there are multiple mechanisms of glia-axon protein transfer. The work described in this research project will show how the stress protein response in nerve tissue can be enhanced. This information may provide a tool that can help to ameliorate the loss of function after central nervous system injury. Potentially, recovery after nervous system trauma could be improved by stimulation of the production of stress proteins or by administering stress proteins. More far-reaching is the possibility that the loss of neurons after physical trauma to the nervous system could be reduced by proper manipulation of the stress protein response.