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February 12, 2026Nature4 citationsOpen Access

Sleep-dependent clearance of brain lipids by peripheral blood cells

BCBumsik ChoDYDiane E. YoungstromSKSamantha Killiany

Key Points

  • The research aims to explore the role of peripheral cells in lipid clearance from the brain during sleep.
  • Identified haemocyte tracking to the brain during sleep in Drosophila.
  • Conducted a screen of phagocytic receptors on haemocytes.
  • Knockdown of the eater receptor to assess effects on sleep and lipid uptake.
  • Eater knockdown reduced sleep duration.
  • Disrupted haemocyte localization to the brain and lipid uptake.
  • Increased brain levels of acetyl-CoA and acetylated proteins had associated impacts on mitochondria.

Abstract

Abstract Sleep is viewed typically through a brain-centric lens, with little known about the role of the periphery 1,2 . Here we identify a sleep function for peripheral macrophage-like cells (haemocytes) in the Drosophila circulation, showing that haemocytes track to the brain during sleep and take up lipids accumulated in cortex glia due to wake-associated oxidative damage. Through a screen of phagocytic receptors expressed in haemocytes, we discovered that knockdown of eater —a member of the Nimrod receptor family—reduces sleep. Loss of eater also disrupts haemocyte localization to the brain and lipid uptake, which results in increased brain levels of acetyl-CoA and acetylated proteins, including mitochondrial proteins PGC1α and DRP1. Dysregulation of mitochondria, reflected in high oxidation and reduced NAD + , is accompanied by impaired memory and lifespan. Thus, peripheral blood cells, which we suggest are precursors of mammalian microglia, perform a daily function of sleep to maintain brain function and fitness.

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Cite This Study

Cho et al. (2026) studied this question.

synapsesocial.com/papers/698d6efe5be6419ac0d54fb3https://doi.org/10.1038/s41586-025-10050-w
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