| Project Area | Glia decoding: deciphering information critical for brain-body interactions |
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| Project/Area Number |
23H04148
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| Research Category |
Grant-in-Aid for Transformative Research Areas (A)
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| Allocation Type | Single-year Grants |
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| Review Section |
Transformative Research Areas, Section (III)
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| Research Institution | University of Tsukuba |
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Principal Investigator |
ラザルス ミハエル 筑波大学, 国際統合睡眠医科学研究機構, 教授 (80469650)
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| Project Period (FY) |
2023-04-01 – 2025-03-31
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| Project Status |
Granted (Fiscal Year 2024)
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| Budget Amount *help |
¥13,000,000 (Direct Cost: ¥10,000,000、Indirect Cost: ¥3,000,000)
Fiscal Year 2024: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2023: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
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| Keywords | Gliosomnia / Immunity / Glia / sleep / glia |
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| Outline of Research at the Start |
Immune cell differentiation and proliferation are known to be synchronized with sleep. However, the molecular and cellular mechanisms by which sleep regulates immune system function and the contribution of glia to the regulation of sleep (gliosomnia) are an enigma. Gene expression in nucleus accumbens glia and leukocytes from wild-type mice, sleep-deprived mice, and mutant mice with high sleep need will be analyzed using single-cell gene expression analysis and identify molecules that interfere with the regulation of the immune system.
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| Outline of Annual Research Achievements |
We successfully demonstrated sleep induction in the NAc of freely behaving mice by increasing the activity of extracellular adenosine derived from astrocytes and neurons with a photoactivatable allosteric modulator of adenosine A2A receptors. We also showed that cytokine production in microglia during wakefulness is important for maintaining wakefulness, demonstrating the importance of glia-mediated neuroimmune interactions in the sleep-wake cycle.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
The paper, "Optochemical control of slow-wave sleep in the nucleus accumbens of male mice by a photoactivatable allosteric modulator of adenosine A2A receptors," has been published in the high-impact journal Nature Communications.
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| Strategy for Future Research Activity |
We continue to perform biochemical and genetic experiments to analyze the function of inflammation-related genes in the NAc. These analyses may help to unravel microglia-neuron interactions in sleep/wake regulation, provide new insights into the link between sleep homeostasis and immune resilience, and identify potential therapeutic targets for the treatment of sleep disorders.
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