2023 Fiscal Year Annual Research Report
Understanding the mechanism of sleepiness by exploring mesolimbic glia-neuron interactions
| Project/Area Number |
21H02802
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| Allocation Type | Single-year Grants |
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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) |
2021-04-01 – 2026-03-31
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| Keywords | Sleep / Glia |
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| Outline of Annual Research Achievements |
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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| 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 accepted for publication in the high-impact journal Nature Communications.
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| Strategy for Future Research Activity |
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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