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Brain Mast Cells in Sleep and Behavioral Regulation
Seiji Nishino1, Noriaki Sakai2, Naoya Nishino2
1Sleep and Circadian Neurobiology Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, CA, USA. nishino@stanford.edu.
Current Topics in Behavioral Neurosciences
|June 17, 2022
Summary
Brain mast cells regulate sleep and wakefulness, with histamine promoting wakefulness. Mast cell deficiency or inhibition improves insomnia and abnormal glycometabolism in a mouse model.
Area of Science:
- Neuroscience
- Immunology
- Sleep Science
Background:
- Mast cells, immune cells found in the brain, release various mediators.
- Their role in neurobehavior and conditions like insomnia and metabolic dysfunction is largely unknown.
- Brain mast cells are constitutively active and respond to diverse stimuli.
Purpose of the Study:
- To investigate the function of brain mast cells in regulating neurobehavior, specifically sleep-wake cycles.
- To explore the involvement of mast cells in a mouse model of chronic insomnia and associated metabolic abnormalities.
- To determine the role of histamine released by mast cells in promoting wakefulness.
Main Methods:
- Utilized mast cell-deficient mice (KitW/KitW-v and Mas-TRECK models).
- Administered diphtheria toxin (DT) to deplete mast cells.
- Induced chronic mild stress (MS) to create an insomnia mouse model.
- Assessed sleep parameters (NREM sleep, fragmentation) and performed glucose/insulin tolerance tests (GTT/ITT).
- Investigated the effects of mast cell inhibitors (cromolyn) and histamine H1 receptor antagonists.
Main Results:
- Mast cell deficiency in mice led to altered sleep/wake phenotypes, with histamine promoting wakefulness.
- DT-induced mast cell depletion reduced wakefulness.
- The MS-induced insomnia model showed increased brain and adipose tissue mast cells.
- Mast cell deficiency or inhibition ameliorated insomnia and abnormal glycometabolism in the MS model.
Conclusions:
- Brain mast cells play a significant role in regulating sleep-wake behavior.
- Histamine released by brain mast cells promotes wakefulness.
- Mast cells are implicated in the pathophysiology of chronic insomnia and associated metabolic dysregulation, suggesting them as a potential therapeutic target.
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