Department of Forensic Analytical Toxicology, School of Forensic Medicine, China Medical University, Shenyang 110122, China.
Liaoning Province Key Laboratory of Forensic Bio-Evidence Sciences, China Medical University, Shenyang 110122, China.
Proc Natl Acad Sci U S A. 2024 Nov 5;121(45):e2400024121. doi: 10.1073/pnas.2400024121. Epub 2024 Nov 1.
Mechanisms controlling the movement of the cerebrospinal fluid (CSF) toward peripheral nerves are poorly characterized. We found that, in addition to the foramina Magendie and Luschka for CSF flow toward the subarachnoid space and glymphatic system, CSF outflow could also occur along periaxonal spaces (termed "PAS pathway") from the spinal cord to peripheral organs, such as the liver and pancreas. When interrogating the latter route, we found that serotonin, acting through 5-HT receptors expressed in ependymocytes that line the central canal, triggered Ca signals to induce polymerization of F-actin, a cytoskeletal protein, to reduce the volume of ependymal cells. This paralleled an increased rate of PAS-mediated CSF redistribution toward peripheral organs. In the liver, CSF was received by hepatic stellate cells. CSF efflux toward peripheral organs through the PAS pathway represents a mechanism dynamically connecting the nervous system with the periphery. Our findings are compatible with the traditional theory of CSF efflux into the glymphatic system to clear metabolic waste from the cerebral parenchyma. Thus, we extend the knowledge of CSF flow and expand the understanding of connectivity between the CNS and peripheral organs.
控制脑脊液（CSF）向周围神经移动的机制尚未得到充分描述。我们发现，除了 Magendie 和 Luschka 孔用于 CSF 流向蛛网膜下腔和神经淋巴系统外，CSF 还可以沿着脊髓到外周器官（称为“PAS 途径”）的轴周间隙流出，如肝脏和胰腺。当我们研究后一种途径时，发现血清素通过在中央管内排列的室管膜细胞表达的 5-HT 受体，触发 Ca 信号诱导肌动蛋白聚合，一种细胞骨架蛋白，以减少室管膜细胞的体积。这与 PAS 介导的 CSF 向周围器官重新分布的速度增加相一致。在肝脏中，CSF 被肝星状细胞接收。CSF 通过 PAS 途径向周围器官流出，代表了一种将神经系统与外周动态连接的机制。我们的发现与 CSF 流入神经淋巴系统以清除脑实质代谢废物的传统理论是一致的。因此，我们扩展了 CSF 流动的知识，并扩大了对中枢神经系统和外周器官之间连通性的理解。
