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  2. Microglia synchronizes with the circadian rhythm of the glymphatic system and modulates glymphatic system function

Microglia synchronizes with the circadian rhythm of the glymphatic system and modulates glymphatic system function

  • IUBMB Life. 2024 Sep 2. doi: 10.1002/iub.2903.
Ting Yang 1 Yan Tang 2 Xinghua Liu 3 4 Song Gong 3 4 Ensheng Yao 1
Affiliations

Affiliations

  • 1 Department of Neurology, The First Affiliated Hospital of Shihezi University, Shihezi, Xinjiang, China.
  • 2 Department of Geriatric, The First Affiliated Hospital of Shihezi University, Shihezi, Xinjiang, China.
  • 3 Division of Trauma Surgery, Emergency Surgery & Surgical Critical, Tongji Trauma Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 4 Department of Emergency and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Abstract

Microglia, as immune cells in the central nervous system, possess the ability to adapt morphologically and functionally to their environment. Glymphatic system, the principal waste clearance system in the brain, exhibits circadian rhythms. However, the impact of microglia on the glymphatic system function remains unknown. In this study, we explored the intricate relationship between microglia and the glymphatic system. Examining diurnal patterns, we identified synchronized behaviors in glymphatic activity and microglial morphology, peaking during sleep and exhibiting distinct changes in branching complexity. Depleting microglia using PLX5622 or in P2Y12 knockout mice enhanced glymphatic function. Chemogenetic manipulation of microglia demonstrated that activating HM3D improved glymphatic function, while inhibiting HM4D unexpectedly increased microglial complexity. These findings highlight the dynamic influence of microglia on the glymphatic system.

Keywords

P2Y12; chemogenetics; circadian rhythms; glymphatic system; microglia.

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