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Narcolepsy susceptibility gene CCR3 modulates sleep-wake patterns in mice
Hiromi Toyoda1,2, Yoshiko Honda2, Susumu Tanaka3
1Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Plos One
|November 30, 2017
Summary
Chemokine receptor 3 (CCR3) plays a role in narcolepsy. Ccr3 knockout mice show abnormal sleep patterns and reduced hypocretin neurons, suggesting CCR3 involvement in narcolepsy pathogenesis.
Area of Science:
- Neuroscience
- Immunology
- Sleep Medicine
Background:
- Narcolepsy is linked to hypocretin (Hcrt) neuron loss and immune system dysfunction.
- Chemokine (C-C motif) receptor 3 (CCR3) is identified as a narcolepsy susceptibility gene.
Purpose of the Study:
- To investigate the role of CCR3 in narcolepsy by examining sleep-wake patterns in Ccr3 knockout (KO) mice.
- To determine the impact of CCR3 deficiency on hypocretin neuron number and response to inflammatory stimuli.
Main Methods:
- Sleep-wake patterns of Ccr3 KO and wild-type (WT) mice were analyzed.
- Mice were administered lipopolysaccharide (LPS) to assess immune-induced sleep changes.
- Hypocretin neuron counts were performed in the lateral hypothalamus.
Main Results:
- Ccr3 KO mice exhibited fragmented sleep during the light phase.
- LPS administration caused exaggerated sleep disturbances in Ccr3 KO mice compared to WT mice, particularly in the light phase.
- Ccr3 KO mice had a reduced number of hypocretin neurons.
Conclusions:
- CCR3 deficiency leads to altered sleep-wake regulation and hypocretin neuron loss.
- These findings suggest a significant role for CCR3 in the pathophysiology of narcolepsy.
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