論文 - 詳細
| RRC ID | 12113 |
|---|---|
| 著者 | Appelbaum L, Wang GX, Maro GS, Mori R, Tovin A, Marin W, Yokogawa T, Kawakami K, Smith SJ, Gothilf Y, Mignot E, Mourrain P. |
| タイトル | Sleep-wake regulation and hypocretin-melatonin interaction in zebrafish. |
| ジャーナル | Proc Natl Acad Sci U S A |
| Abstract |
In mammals, hypocretin/orexin (HCRT) neuropeptides are important sleep-wake regulators and HCRT deficiency causes narcolepsy. In addition to fragmented wakefulness, narcoleptic mammals also display sleep fragmentation, a less understood phenotype recapitulated in the zebrafish HCRT receptor mutant (hcrtr-/-). We therefore used zebrafish to study the potential mediators of HCRT-mediated sleep consolidation. Similar to mammals, zebrafish HCRT neurons express vesicular glutamate transporters indicating conservation of the excitatory phenotype. Visualization of the entire HCRT circuit in zebrafish stably expressing hcrt:EGFP revealed parallels with established mammalian HCRT neuroanatomy, including projections to the pineal gland, where hcrtr mRNA is expressed. As pineal-produced melatonin is a major sleep-inducing hormone in zebrafish, we further studied how the HCRT and melatonin systems interact functionally. mRNA level of arylalkylamine-N-acetyltransferase (AANAT2), a key enzyme of melatonin synthesis, is reduced in hcrtr-/- pineal gland during the night. Moreover, HCRT perfusion of cultured zebrafish pineal glands induces melatonin release. Together these data indicate that HCRT can modulate melatonin production at night. Furthermore, hcrtr-/- fish are hypersensitive to melatonin, but not other hypnotic compounds. Subthreshold doses of melatonin increased the amount of sleep and consolidated sleep in hcrtr-/- fish, but not in the wild-type siblings. These results demonstrate the existence of a functional HCRT neurons-pineal gland circuit able to modulate melatonin production and sleep consolidation. |
| 巻・号 | 106(51) |
| ページ | 21942-7 |
| 公開日 | 2009-12-22 |
| DOI | 10.1073/pnas.906637106 |
| PII | 906637106 |
| PMID | 19966231 |
| PMC | PMC2799794 |
| MeSH | Animals Intracellular Signaling Peptides and Proteins / physiology* Melatonin / biosynthesis Melatonin / physiology* Neuropeptides / physiology* Orexin Receptors Orexins Pineal Gland / metabolism Receptors, G-Protein-Coupled / genetics Receptors, G-Protein-Coupled / metabolism Receptors, G-Protein-Coupled / physiology Receptors, Neuropeptide / genetics Receptors, Neuropeptide / metabolism Receptors, Neuropeptide / physiology Sleep* Wakefulness* Zebrafish / physiology* |
| IF | 9.412 |
| 引用数 | 117 |
| WOS 分野 | NEUROSCIENCES |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ゼブラフィッシュ | tol2 technique? |