Ectopic overexpression of orexin alters sleep/wakefulness states and muscle tone regulation during REM sleep in mice
| Autor: | Megumi Shibahara, Masashi Yanagisawa, Mika Nomiyama, Junko Hara, Jon T. Willie, Hitomi Takahira, Takeshi Sakurai |
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| Rok vydání: | 2010 |
| Předmět: |
medicine.medical_specialty
Population Neuropeptide Sleep REM Mice Transgenic Cellular and Molecular Neuroscience Muscle tone Mice Internal medicine mental disorders Medicine Animals Humans Protein Precursors Wakefulness education Neuroscience of sleep education.field_of_study Orexins business.industry Electromyography Neuropeptides Intracellular Signaling Peptides and Proteins Electroencephalography General Medicine medicine.disease Orexin Rats medicine.anatomical_structure Endocrinology nervous system Muscle Tonus Sleep onset business psychological phenomena and processes Narcolepsy |
| Zdroj: | Journal of molecular neuroscience : MN. 43(2) |
| ISSN: | 1559-1166 |
| Popis: | Orexins (also called hypocretins), which are neuropeptides exclusively expressed by a population of neurons specifically localized in the lateral hypothalamic area, are critically implicated in the regulation of sleep/wake states. Orexin deficiency results in narcoleptic phenotype in rodents, dogs, and humans, suggesting that orexins are important for maintaining consolidated wakefulness states. However, the physiological effect of constitutive increased orexinergic transmission tone, which might be important for understanding the effects of orexin agonists that are promising candidates for therapeutic agents of narcolepsy, has not been fully characterized. We report here the sleep/wakefulness abnormalities in transgenic mice that exhibit widespread overexpression of a rat prepro-orexin transgene driven by a β-actin/cytomegalovirus hybrid promoter (CAG/orexin transgenic mice). CAG/orexin mice exhibit sleep abnormalities with fragmentation of non-rapid eye movement (REM) sleep episode and a reduction in REM sleep. Non-REM sleep was frequently disturbed by short episodes of wakefulness. EEG/EMG studies also reveal incomplete REM sleep atonia with abnormal myoclonic activity during this sleep stage. These results suggest that endogenous orexinergic activity should be appropriately regulated for normal maintenance of sleep states. Orexinergic transmission should be activated during wakefulness, while it should be inactivated or decreased during sleep state to maintain appropriate vigilance states. |
| Databáze: | OpenAIRE |
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