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Published on: January 25, 2016
Mice Lacking Alternatively Activated (M2) Macrophages Show Impairments in Restorative Sleep after Sleep Loss and in
Ashley Massie1, Erin Boland1, Levente Kapás1,2
1Elson S. Floyd College of Medicine, Department of Biomedical Sciences, Washington State University, Spokane, Washington, USA.
Abstract:
The relationship between sleep, metabolism and immune functions has been described, but the cellular components of the interaction are incompletely identified. We previously reported that systemic macrophage depletion results in sleep impairment after sleep loss and in cold environment. These findings point to the role of macrophage-derived signals in maintaining normal sleep. Macrophages exist either in resting form, classically activated, pro-inflammatory (M1) or alternatively activated, anti-inflammatory (M2) phenotypes. In the present study we determined the contribution of M2 macrophages to sleep signaling by using IL-4 receptor α-chain-deficient [IL-4Rα knockout (KO)] mice, which are unable to produce M2 macrophages. Sleep deprivation induced robust increases in non-rapid-eye-movement sleep (NREMS) and slow-wave activity in wild-type (WT) animals. NREMS rebound after sleep deprivation was ~50% less in IL-4Rα KO mice. Cold exposure induced reductions in rapid-eye-movement sleep (REMS) and NREMS in both WT and KO mice. These differences were augmented in IL-4Rα KO mice, which lost ~100% more NREMS and ~25% more REMS compared to WTs. Our finding that M2 macrophage-deficient mice have the same sleep phenotype as mice with global macrophage depletion reconfirms the significance of macrophages in sleep regulation and suggests that the main contributors are the alternatively activated M2 cells.
Insights
Alternatively activated M2 macrophages are crucial for normal sleep regulation. Mice lacking M2 macrophages show impaired sleep rebound after deprivation and exaggerated sleep loss in cold, highlighting their role in maintaining sleep homeostasis.
Area of Science:
- Immunology
- Neuroscience
- Sleep Science
Background:
- The intricate links between sleep, metabolism, and immunity are recognized, yet the specific cellular mechanisms remain unclear.
- Previous research indicated that systemic macrophage depletion impairs sleep following deprivation and cold exposure, suggesting macrophage-derived signals are vital for sleep maintenance.
Purpose of the Study:
- To investigate the specific contribution of alternatively activated M2 macrophages to sleep regulation.
- To elucidate the role of M2 macrophages in mediating sleep responses to challenges like sleep deprivation and cold exposure.
Main Methods:
- Utilized interleukin-4 receptor alpha-chain knockout (IL-4Rα KO) mice, which are deficient in M2 macrophage production.
- Compared sleep patterns (non-rapid-eye-movement sleep [NREMS] and rapid-eye-movement sleep [REMS]) in IL-4Rα KO and wild-type (WT) mice under conditions of sleep deprivation and cold exposure.
Main Results:
- IL-4Rα KO mice exhibited approximately 50% less NREMS rebound after sleep deprivation compared to WT mice.
- Both WT and KO mice experienced sleep reductions during cold exposure, but KO mice showed significantly greater losses in both NREMS (~100% more) and REMS (~25% more).
Conclusions:
- M2 macrophages play a critical role in the regulation of sleep homeostasis.
- The findings suggest that alternatively activated M2 macrophages are the primary macrophage subset responsible for mediating sleep responses to environmental and physiological challenges.
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