A functional role of meningeal lymphatics in sex difference of stress susceptibility in mice

作者：Wei-Ping Dai, Mengqian Yang, Pei Xia, Chuan Xiao, Shuying Huang, Zhan Zhang, Xin Cheng, Wenchang Li, Jian Jin, Jingyun Zhang, Binghuo Wu, Yingying Zhang, Yingying Zhang, Pei-hui Wu, Yangyang Lin, Wen Wu, Hu Zhao, Yan Zhang, Yan Zhang, Wei‐Jye Lin, Xiaojing Ye · 发表于：Nature Communications · 年份：2022 · DOI：10.1038/s41467-022-32556-x · 被引用次数：51 · 研究领域：Cerebrospinal fluid and hydrocephalus、Neuroscience of respiration and sleep、Traumatic Brain Injury Research

Major depressive disorder is one of the most common mental health conditions. Meningeal lymphatics are essential for drainage of molecules in the cerebrospinal fluid to the peripheral immune system. Their potential role in depression-like behaviour has not been investigated. Here, we show in mice, sub-chronic variable stress as a model of depression-like behaviour impairs meningeal lymphatics in females but not in males. Manipulations of meningeal lymphatics regulate the sex difference in the susceptibility to stress-induced depression- and anxiety-like behaviors in mice, as well as alterations of the medial prefrontal cortex and the ventral tegmental area, brain regions critical for emotional regulation. Together, our findings suggest meningeal lymphatic impairment contributes to susceptibility to stress in mice, and that restoration of the meningeal lymphatics might have potential for modulation of depression-like behaviour.