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Published on: April 13, 2017
Microglia synchronizes with the circadian rhythm of the glymphatic system and modulates glymphatic system function
Ting Yang1, Yan Tang2, Xinghua Liu3,4
1Department of Neurology, The First Affiliated Hospital of Shihezi University, Shihezi, Xinjiang, 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.
Insights
Microglia (immune cells in the brain) influence the glymphatic system (waste clearance). Their depletion or specific manipulation enhances brain waste removal, particularly during sleep.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia are the primary immune cells of the central nervous system, exhibiting remarkable morphological and functional plasticity.
- The glymphatic system, responsible for brain waste clearance, operates with distinct circadian rhythms.
- The precise role of microglia in modulating glymphatic system function remains largely unexplored.
Purpose of the Study:
- To investigate the relationship between microglia and glymphatic system function.
- To examine the diurnal patterns of microglial morphology and glymphatic activity.
- To determine the impact of microglial modulation on glymphatic clearance efficiency.
Main Methods:
- Observation of diurnal patterns in microglial morphology and glymphatic activity.
- Pharmacological depletion of microglia using PLX5622.
- Genetic depletion of microglia in P2Y12 knockout mice.
- Chemogenetic manipulation of microglia using HM3D and HM4D DREADDs.
Main Results:
- Microglial morphology and glymphatic activity exhibit synchronized diurnal patterns, peaking during sleep.
- Depletion of microglia significantly enhanced glymphatic system function.
- Chemogenetic activation of microglia (HM3D) improved glymphatic function, while inhibition (HM4D) paradoxically increased microglial complexity.
- P2Y12 knockout mice, lacking specific microglial populations, showed enhanced glymphatic function.
Conclusions:
- Microglia exert a dynamic and significant influence on the functional capacity of the glymphatic system.
- Modulating microglial activity presents a potential therapeutic avenue for enhancing brain waste clearance.
- The interplay between microglial state and glymphatic function is crucial for maintaining brain homeostasis.
