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

• Published in: Nature communications Vol. 13; no. 1; p. 4825
• Main Authors: Dai, Weiping, Yang, Mengqian, Xia, Pei, Xiao, Chuan, Huang, Shuying, Zhang, Zhan, Cheng, Xin, Li, Wenchang, Jin, Jian, Zhang, Jingyun, Wu, Binghuo, Zhang, Yingying, Wu, Pei-hui, Lin, Yangyang, Wu, Wen, Zhao, Hu, Zhang, Yan, Lin, Wei-Jye, Ye, Xiaojing
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 16-08-2022; Nature Publishing Group; Nature Portfolio
• Subjects: 13/109; 14/1; 14/19; 14/34; 14/35; 14/63; 49/91; 631/378/1457/1945; 631/378/1831; 64/60; 82/80; 96/31; Anxiety; Cerebrospinal fluid; Humanities and Social Sciences; Immune system; Mental depression; Mental disorders; Mental health; multidisciplinary; Prefrontal cortex; Science; Science (multidisciplinary); Sex differences; Sexual behavior; Stress; Susceptibility; Ventral tegmentum
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-32556-x

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.
The mechanisms underlying sex differences in response to stress are unclear. Here, the authors show that meningeal lymphatics dysfunction modulates the sex difference in the stress susceptibility to depression- and anxiety-like behaviours in mice.