The role of oligodendroglial exosome secretion in axon-glia communication, glial support, and maintenance of axonal integrity

少突胶质细胞构建中枢神经系统髓鞘，并为负责长期轴突维持的神经元提供营养支持（胶质支持）。神经胶质支持的丧失导致轴突进行性变性，并解释了许多髓鞘疾病的不可逆转过程。我们发现少突胶质细胞释放称为外泌体的细胞外囊泡，其具有向神经元传递生物学功能分子并赋予应激保护的能力。在这个项目中，我们将阐明外泌体在神经元-胶质细胞通讯和胶质细胞支持中的作用。我们将利用转基因小鼠模型在体外和体内研究少突胶质细胞-神经元外泌体转移对功能的影响。外泌体中富集的微rna在神经元靶基因水平调控中的作用将被研究。我们的目标是探索外泌体促进轴突维持和维持其完整性的分子机制。这项研究将有助于确定目标分子，这些目标分子可能用于治疗髓鞘疾病以及其他神经退行性疾病，以防止轴突损失。

Oligodendrocytes build the central nervous system myelin sheath and in addition provide trophic support to neurons responsible for long-term axonal maintenance (glial support). Loss of glial support results in progressive degeneration of axons and accounts for the irreversible course of many myelin diseases. We have discovered that oligodendrocytes release extracellular vesicles termed exosomes, which have the ability to deliver biologically functional molecules to neurons and confer stress protection. In this project we will elucidate the role of exosomes in neuron-glia communication and glial support. We will study the functional impact of oligodendrocyte-neuron exosome transfer in vitro and in vivo utilizing transgenic mouse models. The role of micro-RNAs enriched in exosomes in horizontal regulation of neuronal target genes will be investigated. Our goal is to explore the molecular mechanisms that exosomes employ to facilitate axonal maintenance and sustain their integrity. This study will help to define target molecules that may be therapeutically addressed to prevent axon loss in myelin diseases as well other neurodegenerative diseases.