Meningeal lymphatics-microglia axis regulates synaptic physiology

Meningeal lymphatics serve as an outlet for cerebrospinal fluid, and their dysfunction is associated with various neurodegenerative conditions. Previous studies have demonstrated that dysfunctional meningeal lymphatics evoke behavioral changes, but the neural mechanisms underlying these changes have remained elusive. Here, we show that prolonged impairment of meningeal lymphatics alters the balance of cortical excitatory and inhibitory synaptic inputs, accompanied by deficits in memory tasks. These synaptic and behavioral alterations induced by lymphatic dysfunction are mediated by microglia, leading to increased expression of the interleukin 6 gene (Il6). IL-6 drives inhibitory synapse phenotypes via a…

• GT
  Genome Technology Access Center

  Award: P30 CA91842
• WU
  Washington University in St. Louis
• IO
  Institute of Clinical and Translational Sciences
• UO
  University of Edinburgh
• UO
  University of Queensland
• NR
  National Research Foundation of Korea

  Award: 2021R1A6A3A14045044
• KA
  Korea Advanced Institute of Science and Technology
• NI
  National Institutes of Health
• NI
  National Institute on Aging

  Awards: AG034113, AG078106
• NC
  National Cancer Institute

  Award: P30 CA91842
• NI
  National Institute of General Medical Sciences

  Awards: P41 GM103422, R24GM136766
• NC
  National Center for Research Resources
• NC
  National Center for Advancing Translational Sciences

  Award: UL1 TR000448