Sun Yat-sen University Ye Xiaojing's team revealed that stress is more likely to cause female meningeal lymphatic disorder

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The central nervous system has long been considered an "immune-privileged" organ due to the lack of lymphatic vessels that transport immune cells

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Stress induces disorders of meningeal lymphatic vessels in female mice

The researchers found that the subchronic variable stress model caused female mice to exhibit depression-like and anxiety-like behaviors, but male mice did not exhibit depression-like behavioral disorders

Figure 1: Stress damages dural structures in female mice

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Meningeal lymphatic disorder promotes stress sensitivity

It has been shown that vascular endothelial growth factor-C (VEGFC) is a secreted protein that binds to vascular endothelial growth factor receptor 3 (VEGFR3), which is mainly expressed on LECs, to promote the growth of lymphatic vessels

Figure 2: Meningeal lymphatic disorder promotes stress sensitivity in male mice

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Molecular mechanism of meningeal lymphatic disorder

In order to further understand the molecular mechanism of gender differences in dural lymphatic vessels caused by sub-stress, the researchers used single-cell sequencing technology to change the genes of dural lymphatic endothelial cells in female mice after stress, mainly involving DNA replication, sphingomyelin biosynthesis, serotonin uptake and other signaling pathways, and found that 236 differentially expressed genes were enriched (156 up-regulated, 80 down-regulated), among which the dissociation of extracellular matrix may be a key biological event mediating meningeal lymphatic function

Figure 3: Inhibition of Ccl6 signaling alleviates stress-induced depression-like behaviors

Summarize

Since the discovery of the meningeal lymphatic vessels in 2015, multiple lines of evidence point to disorders in Alzheimer's, Parkinson's, brain tumors and other neurological diseases

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