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

Weiping Dai, Mengqian Yang, Pei Xia, Chuan Xiao, Shuying Huang, Zhan Zhang, Xin Cheng, Wenchang Li, Jian Jin, Jingyun Zhang, Binghuo Wu, Yingying Zhang, Pei-hui Wu, Yangyang Lin, Wen Wu, Hu Zhao, Yan Zhang (), Wei-Jye Lin () and Xiaojing Ye ()
Additional contact information
Weiping Dai: Sun Yat-sen University
Mengqian Yang: Sun Yat-sen University
Pei Xia: Sun Yat-sen University
Chuan Xiao: Sun Yat-sen University
Shuying Huang: Sun Yat-sen University
Zhan Zhang: Sun Yat-sen University
Xin Cheng: Sun Yat-sen University
Wenchang Li: Sun Yat-sen University
Jian Jin: Southern Medical University
Jingyun Zhang: Sun Yat-sen University
Binghuo Wu: Sun Yat-sen University, Ministry of Education
Yingying Zhang: Sun Yat-sen University
Pei-hui Wu: Sun Yat-sen University
Yangyang Lin: Sun Yat-sen University
Wen Wu: Southern Medical University
Hu Zhao: Sun Yat-sen University
Yan Zhang: Central South University
Wei-Jye Lin: Sun Yat-sen University
Xiaojing Ye: Sun Yat-sen University

Nature Communications, 2022, vol. 13, issue 1, 1-21

Abstract: Abstract 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.

Date: 2022
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DOI: 10.1038/s41467-022-32556-x

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