Neuron Glial Interactions

描述（由申请人提供）：影响嗅觉神经持续替代嗅觉感觉神经元轴突的能力的机制尚不清楚。最近的数据，从我们的实验室和其他人，强调神经胶质细胞的作用，包裹轴突束的神经，嗅鞘细胞/神经胶质细胞（OECs）。我们以前表明，嗅鞘细胞支持轴突生长，描述了它们的一些基本分子特性，并证明了它们作为脊髓损伤移植策略的有效性。在当前的应用中，我们提出了一系列的研究，以检查之间的沟通机制的嗅鞘细胞和轴突和嗅鞘细胞。在神经系统的其他地方描述的胶质细胞-神经元相互作用提供了一种协调和同步活动的机制。在嗅觉通路中，神经元-胶质细胞的相互作用可以提供一种策略，用于控制生长因子或其他分子的释放，这些分子可能有助于嗅鞘细胞对轴突延伸的营养作用。为了实现这一总体假设，我们提出了一系列3个目标。首先，我们将测试的假设，谷氨酸的机制，包括谷氨酸受体和/或转运，由嗅鞘细胞表达。我们还将定量间隙连接蛋白的表达及其在该通路中的分布。最后，同步损失和更换轴突对这些属性的影响将被检查。其次，OEC的基本生物物理特性及其对轴突释放的谷氨酸的反应尚未研究。我们的初步数据表明可能发生动态相互作用，并且OEC可以支持响应谷氨酸的瞬时膜电流。我们将继续研究这一发现，同时确定这些属性是否在退化/再生事件期间发生变化。第三，嗅鞘细胞增殖/周转的机制是未知的，但也可能受到来自嗅神经的影响;有初步数据表明，嗅鞘细胞可能会增加轴突（再生）生成过程中的增殖，提出假设，即嗅鞘细胞：轴突的比例可能是恢复的决定因素。总的来说，这些研究将对我们理解嗅觉通路中细胞周转和轴突生长的机制产生重大影响;对治疗嗅神经创伤性损伤患者以及建议使用嗅鞘细胞作为脊髓损伤治疗策略的关键信息。

DESCRIPTION (provided by applicant): The mechanisms influencing the capacity of the olfactory nerve for ongoing replacement of olfactory sensory neuron axons is not well understood. Recent data, from our labs and others, emphasize the role of the glia that wrap axon fascicles in the nerve, the olfactory ensheathing cells/glia (OECs). We showed previously that OECs support axon outgrowth, described some of their basic molecular properties, and demonstrated their effectiveness as a transplant strategy in spinal cord injury. In the current application we propose a series of studies to examine mechanisms of communication among OECs and between the axons and OECs. Glia-neuron interactions being described elsewhere in the nervous system provide a mechanism for coordinating and synchronizing activity. In the olfactory pathway, neuron-glia interactions could provide a strategy for governing the release of growth factors or other molecules that may contribute to the trophic effect of OECs on axon extension. To pursue this overarching hypothesis we propose a series of 3 aims. First, we will test the hypothesis that glutamate mechanisms, including glutamate receptors and/or transporters, are expressed by the OECs. We will also quantify gap junction protein expression and their distribution in this pathway. Finally, the effects of synchronized loss and replacement of axons on these properties will be examined. Second, the basic biophysical properties of OECs and their response to glutamate released by axons has not been studied. Our preliminary data suggest a dynamic interaction may occur and that the OECs can support transient membrane currents in response to gluatamate. We will pursue this finding while also determining if these properties change during degenerative/regenerative events. Third, the mechanisms of OEC proliferation/turnover are unknown but may also be subject to influences from the olfactory nerve; there is preliminary data suggesting that OECs may increase proliferation during axon (re)generation raising the hypothesis that the ratio of OECs:axons may be a determinant of recovery. Collectively, these studies will have a significant impact on our understanding of the mechanisms of cell turnover and axon growth in the olfactory pathway; information critical to the treatment of patients with traumatic injury to the olfactory nerve as well as to the proposed use of OECs as a treatment strategy in spinal cord injury.