| 研究課題/領域番号 |
21H02802
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| 配分区分 | 補助金 |
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| 研究機関 | 筑波大学 |
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研究代表者 |
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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| 研究期間 (年度) |
2021-04-01 – 2026-03-31
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| キーワード | Sleep / Glia |
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| 研究実績の概要 |
Brain glial cells may have a much greater influence on sleep homeostasis than previously thought. We have previously shown that the nucleus accumbens (NAc) is a novel brain region involved in sleep regulation, especially non-rapid eye movement sleep, by integrating motivational stimuli. 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. Our experiments demonstrate the potential of in vivo A2AR PAM optochemistry for the treatment of neurological disorders. The use of BBB-permeable photoactivatable A2AR PAMs offers an advantage over conventional neuropharmacological approaches due to the high physiological specificity of allosteric modulation.
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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
2: おおむね順調に進展している
理由
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 accepted for publication in the high-impact journal Nature Communications.
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| 今後の研究の推進方策 |
We continue to perform chemogenetic activation/inhibition of nucleus accumbens microglia and biochemical and genetic experiments to analyze the function of inflammation-related genes in the NAc. These analyses may help to unravel glia-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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