Brain Research Center, Sun Yat-sen Memorial Hospital and Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
Faculty of Forensic Medicine, Guangdong Province Translational Forensic Medicine Engineering Technology Research Center, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
Nat Commun. 2022 Aug 16;13(1):4825. 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.
重度抑郁症是最常见的心理健康问题之一。脑膜淋巴管对于将脑脊液中的分子排出到外周免疫系统至关重要。然而，它们在抑郁症样行为中的潜在作用尚未得到研究。在这里，我们在小鼠中表明，慢性可变应激作为抑郁症样行为的模型，会损害雌性小鼠而非雄性小鼠的脑膜淋巴管。脑膜淋巴管的操作调节了小鼠对应激诱导的抑郁和焦虑样行为易感性的性别差异，以及内侧前额叶皮层和腹侧被盖区的改变，这些脑区对于情绪调节至关重要。总之，我们的研究结果表明脑膜淋巴管的损伤会导致小鼠对压力的易感性，并且脑膜淋巴管的恢复可能对抑郁症样行为具有调节作用。
