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Updated: Aug 21, 2025

Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
09:12

Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates

Published on: January 30, 2014

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Microglial TNFα orchestrates protein phosphorylation in the cortex during the sleep period and controls homeostatic

Maria J Pinto1, Léa Cottin1, Florent Dingli2

  • 1Institut de Biologie de l'École normale supérieure (IBENS), École normale supérieure, CNRS, INSERM, Université PSL, Paris, France.

The EMBO Journal
|November 17, 2022
PubMed

Insights

Microglia regulate sleep need by releasing tumor necrosis factor-alpha (TNFα). This process involves controlling protein phosphorylation in the brain, impacting sleep duration and homeostatic recovery.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Sleep Science

Background:

  • Sleep intensity is regulated by prior wakefulness and homeostatic control via protein phosphorylation.
  • Microglia, the brain's immune cells, were not previously recognized as part of the sleep regulatory circuitry.

Purpose of the Study:

  • To investigate the role of microglia in sleep homeostasis.
  • To identify the molecular mechanisms by which microglia influence sleep regulation.

Main Methods:

  • Quantitative phosphoproteomics was used to analyze the frontal cortex of mice with microglia-specific deletion of tumor necrosis factor-alpha (TNFα).
  • Sleep need was measured using electroencephalogram (EEG) slow-wave activity.

Main Results:

  • Microglia-specific TNFα deletion altered thousands of phosphorylation sites during sleep.
  • Microglial TNFα influences sleep-related kinases (MAPKs, MARKs) and synaptic proteins involved in encoding sleep need.
  • Loss of microglial TNFα reduced the accumulation of sleep need and impaired sleep compensation.

Conclusions:

  • Microglia are a novel cellular component of the sleep homeostasis circuit.
  • Microglial TNFα release modulates neuronal phosphorylation, thereby controlling sleep need and duration.
  • This study reveals a new pathway for sleep regulation involving neuro-immune interactions.
Keywords:
TNFαmicrogliaphosphoproteomesleepsynapse

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