Understanding the mechanism of sleepiness by exploring mesolimbic glia-neuron interactions
| Project/Area Number |
23K21394
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| Project/Area Number (Other) |
21H02802 (2021-2023)
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Multi-year Fund (2024)
Single-year Grants (2021-2023) |
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| Section | 一般 |
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| Review Section |
Basic Section 51020:Cognitive and brain science-related
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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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| Project Status |
Granted (Fiscal Year 2024)
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| Budget Amount *help |
¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
Fiscal Year 2025: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2024: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2023: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2022: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2021: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
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| Keywords | sleep / glia / scRNAseq / Sleep / Glia |
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| Outline of Research at the Start |
The cellular and molecular processes underlying the build-up of sleepiness and maintenance of sleep are unknown. Glia are far from being merely support cells of the brain. The nucleus accumbens, a new sleep-regulating area through the integration of motivational stimuli provides an excellent opportunity to study the regulation of sleep and motivation by glia-neuron interactions.
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| Outline of Annual Research Achievements |
We previously developed the first positive allosteric modulator of adenosine A2A receptors (A2AR), named A2AR PAM-1, that evokes A2AR responses in the brain (e.g., sleep induction) without affecting cardiovascular function, unlike classic A2AR agonists. We are now collaborating with the Abe Lab (Hiroshima University, Graduate School of Advanced Science and Engineering) to develop a visible-light (420 nm) photoactivatable (‘caged’) A2AR PAM-1. Using the opto-version of the A2AR PAM, we, for the first time, optochemically induced sleep in freely behaving mice and demonstrated that extracellular adenosine produced by glia and neurons in nucleus accumbens promotes sleep [Roy K et al., in preparation].
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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
In addition to developing a new tool for optochemical control of extracellular adenosine, we have installed equipment for single-cell gene expression profiling, including a 10X Genomics Controller for feature barcoding, an S2 Singulator 100 for single nuclei preparation, and a workstation for data analysis. We are now able to rapidly generate insights that are critical for understanding glia-neuron interactions during sleep at the molecular level.
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| Strategy for Future Research Activity |
In the future, pharmacotherapy may offer the possibility to cure diseases and alleviate symptoms while preventing uncontrolled drug activity in time and space, i.e. the drug is only active at times and sites where it produces its therapeutic effect. Our approach should aid in the generation of visible-light photocactivatable compounds for virtually any druggable target.
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Report
(1 results)
Research Products
(5 results)
