| 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
|
| リソース情報 |
| ゼブラフィッシュ |
tol2 technique? |
