PDF(Pubmed)
Abstract：
The nervous system is primarily composed of neurons and glia, and the communication between them plays profound roles in regulating the development and function of the brain. Neuron-glia signal transduction is known to be mediated by secreted or juxtacrine signals through ligand-receptor interactions on the cell membrane. Here, we report a novel mechanism for neuron-glia signal transduction, wherein neurons transmit proteins to glia through extracellular vesicles, activating glial signaling pathways. We find that in the amphid sensory organ of Caenorhabditis elegans, different sensory neurons exhibit varying aging rates. This discrepancy in aging is governed by the crosstalk between neurons and glia. We demonstrate that early-aged neurons can transmit heat shock proteins (HSP) to glia via extracellular vesicles. These neuronal HSPs activate the IRE1-XBP1 pathway, further increasing their expression in glia, forming a positive feedback loop. Ultimately, the activation of the IRE1-XBP-1 pathway leads to the transcriptional regulation of chondroitin synthases to protect glia-embedded neurons from aging-associated functional decline. Therefore, our studies unveil a novel mechanism for neuron-glia communication in the nervous system and provide new insights into our understanding of brain aging.
摘要：
神经系统主要由神经元和神经胶质组成，它们之间的交流在调节大脑的发育和功能方面起着深远的作用。已知神经元-神经胶质信号转导通过细胞膜上的配体-受体相互作用由分泌或接近分泌信号介导。这里,我们报道了神经元-神经胶质信号转导的新机制，其中神经元通过细胞外囊泡将蛋白质传递给神经胶质，激活神经胶质信号通路。我们发现在秀丽隐杆线虫的两栖动物感觉器官中,不同的感觉神经元表现出不同的衰老率。衰老的这种差异受神经元和神经胶质之间的串扰控制。我们证明了早期衰老的神经元可以通过细胞外囊泡将热休克蛋白（HSP）传递给神经胶质细胞。这些神经元HSP激活IRE1-XBP1通路，进一步增加它们在胶质细胞中的表达，形成正反馈回路。最终,IRE1-XBP-1通路的激活导致软骨素合酶的转录调节,以保护嵌入神经胶质的神经元免受衰老相关的功能衰退.因此,我们的研究揭示了神经系统中神经元-胶质细胞交流的新机制，并为我们对大脑衰老的理解提供了新的见解。
