Dynamic changes in Olfactory Ensheathing Cell properties after neuronal loss

描述（由申请人提供）：嗅觉有助于提高生活质量，并警告环境中存在的危险。损害这种感官形态的疾病和损伤降低了对外界的认识，使人的生命处于危险之中。嗅觉上皮（OE）直接暴露在环境损伤中，因此发展出了显著的进行广泛再生的能力。即使在正常情况下，嗅觉感觉神经元（OSN）也会进行持续的再生。虽然在正常和再生上皮中对嗅觉神经网络的特性进行了广泛的研究，但在非神经元嗅觉细胞中相关的动态细胞和分子变化在很大程度上尚未被探索。在本提案中，我将研究嗅鞘细胞（OEC）的特性。oec是一种特殊的神经胶质细胞群，只存在于嗅觉系统中。当它们从鼻腔的嗅上皮投射到大脑前部的嗅球时，它们包裹着嗅神经网络的轴突束。它们存在于嗅上皮和大脑中，使oec成为一种独特的胶质细胞，从周围神经系统延伸到中枢神经系统。它们的分子和细胞特性反映了这种杂交作用。据称OECs促进再生的能力使OECs成为治疗脊髓损伤、中风和帕金森病的有吸引力的治疗剂。oec促进体外轴突再生长，并据报道可增强脊髓损伤模型的功能恢复。然而，oec的性质和响应OSN再生的动态变化尚未得到研究。因此，本研究的目的是研究OSN损伤、丢失和再生过程中oec体内发生的分子和细胞变化。该假说的核心假设是，嗅觉感觉神经元的死亡会导致嗅鞘细胞发生关键的分子和细胞变化，从而促进感觉神经元及其轴突的成功再生。因此，在本提案中，我将通过监测基因表达的变化来表征OSN损伤和再生过程中oec的分子和细胞反应。此外，我将描述由于oec丢失而引起的osn的分子和细胞反应。为验证这一假设而提出的实验结果将为我们提供关于OEC生物学的新见解，这将导致OEC作为修复神经元损伤的治疗药物的改进。

DESCRIPTION (provided by applicant): The sense of smell contributes to quality of life and warns of dangers present in the environment. Disease and injury that compromise this sensory modality decreases awareness of the outside world and puts one's life at risk. The olfactory epithelium (OE) is directly exposed to environmental insults and, as a result, developed a remarkable ability to undergo extensive regeneration. Even under normal circumstances, olfactory sensory neurons (OSN) undergo ongoing and continual regeneration. While the properties of OSNs have been extensively studied in normal and regenerating epithelium, the associated dynamic cellular and molecular changes in non-neuronal olfactory cells are largely unexplored. In this proposal, I will examine the properties of olfactory ensheathing cells (OEC). OECs are a special population of glial cells found exclusively in the olfactory system. They ensheath the axon bundles of OSNs as they project from the olfactory epithelium in the nasal cavity into the olfactory bulb at the front of the brain. Their presence in the olfactory epitheliu and the brain makes OECs a unique type of glial cell that span projections from the peripheral nervous system to the CNS. Their molecular and cellular properties reflect this hybrid role. The purported ability of OECs to promote regeneration has made OECs an attractive therapeutic agent for treating spinal cord injury, stroke, and Parkinson's disease. OECs promote axonal re-growth in vitro and are reported to enhance functional recovery in spinal cord injury models. However, the nature and dynamics of OECs change in response to OSN regeneration has not been studied. Therefore, the goal of this proposal is to study molecular and cellular changes that take place in vivo in OECs during OSN injury, loss, and regeneration. The central hypothesis of this proposal is that the death of olfactory sensory neurons causes critical molecular and cellular changes in olfactory ensheathing cells that encourage successful re- growth of sensory neurons and their axons. Therefore, in this proposal, I will characterize the molecular and cellular responses of OECs during OSN injury and regeneration by monitoring changes in gene expression. Moreover, I will characterize molecular and cellular responses of OSNs due to loss of OECs. The results of the experiments proposed to test this hypothesis will provide us with new insights on the OEC biology, which will lead to improvement of OECs as therapeutic agents for repairing neuronal injury.