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: 8656099
• 负责人: Tanu Sharma
• 金额: $ 4.27万
• 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 2015-05-23
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8656099
• 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; Gene Expression Profiling; 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.

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对外部世界的认识，并使人的生命处于危险之中。嗅上皮（OE）直接暴露于环境的侮辱，因此，开发了一个显着的能力，进行广泛的再生。即使在正常情况下，嗅觉感觉神经元（OSN）也会持续不断地再生。虽然在正常和再生上皮中已经广泛研究了OSN的性质，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探索。在这篇论文中，我将研究嗅鞘细胞（OEC）的特性。嗅鞘细胞是一种特殊的神经胶质细胞群，只存在于嗅觉系统中。当OSN从鼻腔中的嗅上皮投射到大脑前部的嗅球时，它们包裹OSN的轴突束。它们在嗅上皮和脑中的存在使得OECs成为一种独特类型的神经胶质细胞，其跨越从外周神经系统到CNS的投射。它们的分子和细胞特性反映了这种混合作用。据称OECs促进再生的能力使得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。嗅鞘细胞在体外促进轴突再生，并据报道可增强脊髓损伤模型的功能恢复。然而，OECs响应OSN再生的性质和动力学变化尚未研究。因此，本提案的目标是研究OSN损伤、丢失和再生期间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引起嗅觉鞘细胞中的关键分子和细胞变化，这些变化促进感觉神经元及其轴突的成功再生长。因此，在这个建议中，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OECs的分子和细胞反应。此外，我将表征OSN的分子和细胞反应，由于OECs的损失。实验结果表明，OEC具有良好的生物学特性，可作为神经元损伤修复的治疗药物。