| 研究課題/領域番号 |
17H02215
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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, 准教授 (80469650)
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| 研究分担者 |
高田 陽子 筑波大学, 国際統合睡眠医科学研究機構, 研究員 (60435740)
斉藤 毅 筑波大学, 国際統合睡眠医科学研究機構, 助教 (80609933)
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| 研究期間 (年度) |
2017-04-01 – 2021-03-31
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| キーワード | Sleep / Motivation / Nucleus accumbens |
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| 研究実績の概要 |
Sleep and wakefulness are controlled by a wide range of neuronal populations in the mammalian brain.
Activation of adenosine A2A receptor (A2AR)-expressing neurons in the nucleus accumbens (NAc) core promotes slow-wave sleep (SWS). The neuronal mechanism by which activation of NAc A2AR neurons induces SWS, however, is unknown. We hypothesized that the ability of NAc activation to induce sleep is mediated by the classic somnogen adenosine. To investigate whether astrocytes are involved in the ability of the NAc to regulate SWS, we ablated glial fibrillary acidic protein (GFAP)-positive cells in the NAc core of mice by virus-mediated expression of diphtheria toxin (DT) receptors and intraperitoneal administration of DT. Analysis of electroencephalogram and electromyogram recordings of DT-treated wild-type mice revealed that SWS was remarkably increased at 1 week after DT treatment, whereas sleep-wake behavior was unchanged in DT-treated A2AR knockout mice. Cell ablation was associated with an increased number of GFAP-positive cells and activation of microglia in the NAc. In-vivo microdialysis revealed significantly increased levels of extracellular adenosine in the NAc at 1 week after DT treatment. Our findings suggest that elevated adenosine levels in the NAc core promote SWS by acting on A2ARs and provide the first evidence that adenosine is an endogenous candidate for activating NAc A2AR neurons that have the ability to induce SWS.
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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 project is progressing well and further results of this project have been published in the journal Neurochemistry International.
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| 今後の研究の推進方策 |
We will continue to elucidate the mechanism of the activation of the NAc for sleep control. Glial cells, including astrocytes, may play an important role in regulating extracellular adenosine in the NAc during sleep and wakefulness.
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