Dynamic changes in Olfactory Ensheathing Cell properties after neuronal loss

神经元丢失后嗅鞘细胞特性的动态变化

• 批准号: 8397321
• 负责人: Tanu Sharma
• 金额: $ 4.22万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-05-25 至 2015-05-24
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8397321
• 关键词: A Mouse; Ablation; Afferent Neurons; Affinity; Awareness; Axon; Biology; Brain; Cell Communication; Cells; Cellular biology; Cessation of life; Collecting Cell; Diphtheria Toxin; Disease; Down-Regulation; DsRed; Environment; Epithelium; Gases; Gene Expression; Genes; Genetic Programming; Goals; Growth; Histologic; Hybrids; In Vitro; Individual; Injury; Lamina Propria; Lead; Lesion; Life; Mediating; Microarray Analysis; Modality; Modeling; Molecular; Monitor; Mus; Nasal cavity; Natural regeneration; Nature; Nervous system structure; Neuraxis; Neuroglia; Neuronal Injury; Neurons; Olfactory Epithelium; Olfactory Mucosa; Parkinson Disease; Pathway interactions; Peripheral; Peripheral Nervous System; Population; Process; Property; Proteins; Quality of life; Recovery; Recovery of Function; Reporting; Risk; Role; Sensory; Signal Pathway; Smell Perception; Spinal cord injury; Staging; Stroke; System; Tamoxifen; Testing; Therapeutic Agents; Time; Transgenic Mice; Transgenic Organisms; Up-Regulation; cell type; diphtheria toxin receptor; in vivo; injured; insight; methyl bromide; named group; neuron loss; neuronal cell body; olfactory bulb; promoter; receptor; repaired; research study; response; selective expression

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. PUBLIC HEALTH RELEVANCE: In the olfactory system, sensory neurons are closely associated with a cell type called olfactory ensheathing cells (OECs). OECs are a special population of glial cells in the nervous system shown to promote re-growth of certain injured neurons. Therefore, the main aim of this proposal is to gain new insights on the biology of OEC, in order to make improvements to OECs as therapeutic agents for repairing neuronal injury caused by, for example, stroke, physical injury, and Parkinson's disease.

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。损害这种感觉方式的疾病和伤害会降低人们对外界的认识，并使人的生命处于危险之中。嗅觉上皮（OE）直接暴露于环境侵害，因此发展出非凡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）也会持续再生。虽然 OSN 的特性已在正常和再生上皮中进行了广泛研究，但非神经元嗅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 是仅在嗅觉系统中发现的特殊神经胶质细胞群。当 OSN 从鼻腔的嗅觉上皮投射到大脑前部的嗅球时，它们会包裹 OSN 的轴突束。它们存在于嗅觉上皮和大脑中，使 OEC 成为一种独特类型的神经胶质细胞，其投射范围涵盖从周围神经系统到中枢神经系统。它们的分子和细胞特性反映了这种混合作用。 OEC 据称具有促进再生的能力，这使得 OEC 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 在体外促进轴突再生长，据报道可增强脊髓损伤模型的功能恢复。然而，OEC 响应 OSN 再生而变化的性质和动态尚未得到研究。因此，本提案的目标是研究 OSN 损伤、丢失和再生过程中 OEC 体内发生的分子和细胞变化。该提议的中心假设是，嗅觉感觉神经元的死亡会导致嗅觉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 丢失而导致的 OSN 的分子和细胞反应。为检验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剂的改进。 公共健康相关性：在嗅觉系统中，感觉神经元与一种称为嗅鞘细胞 (OEC) 的细胞类型密切相关。 OEC 是神经系统中的一种特殊神经胶质细胞群，可促进某些受损神经元的重新生长。因此，该提案的主要目的是获得对 OEC 生物学的新见解，以改进 OEC 作为修复由中风、身体损伤和帕金森病等引起的神经元损伤的治疗剂。