Cerebral mGluR5 availability contributes to elevated sleep need and behavioral adjustment after sleep deprivation.

Details

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State: Public
Version: Final published version
Serval ID
serval:BIB_BBCD63F1F691
Type
Article: article from journal or magazin.
Collection
Publications
Title
Cerebral mGluR5 availability contributes to elevated sleep need and behavioral adjustment after sleep deprivation.
Journal
eLife
Author(s)
Holst S.C., Sousek A., Hefti K., Saberi-Moghadam S., Buck A., Ametamey S.M., Scheidegger M., Franken P., Henning A., Seifritz E., Tafti M., Landolt H.P.
ISSN
2050-084X (Electronic)
ISSN-L
2050-084X
Publication state
Published
Issued date
05/10/2017
Peer-reviewed
Oui
Volume
6
Pages
eLife.28751
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Abstract
Increased sleep time and intensity quantified as low-frequency brain electrical activity after sleep loss demonstrate that sleep need is homeostatically regulated, yet the underlying molecular mechanisms remain elusive. We here demonstrate that metabotropic glutamate receptors of subtype 5 (mGluR5) contribute to the molecular machinery governing sleep-wake homeostasis. Using positron emission tomography, magnetic resonance spectroscopy, and electroencephalography in humans, we find that increased mGluR5 availability after sleep loss tightly correlates with behavioral and electroencephalographic biomarkers of elevated sleep need. These changes are associated with altered cortical myo-inositol and glycine levels, suggesting sleep loss-induced modifications downstream of mGluR5 signaling. Knock-out mice without functional mGluR5 exhibit severe dysregulation of sleep-wake homeostasis, including lack of recovery sleep and impaired behavioral adjustment to a novel task after sleep deprivation. The data suggest that mGluR5 contribute to the brain's coping mechanisms with sleep deprivation and point to a novel target to improve disturbed wakefulness and sleep.
Keywords
Animals, Brain/physiology, Brain Chemistry, Gene Knockout Techniques, Homeostasis, Mice, Mice, Knockout, Receptor, Metabotropic Glutamate 5/genetics, Receptor, Metabotropic Glutamate 5/metabolism, Sleep, Sleep Deprivation, Wakefulness, PET-MRS, Y-maze, fragile X syndrome, human, molecular imaging, mouse, neuroscience, plasticity marker, working memory
Pubmed
Web of science
Open Access
Yes
Create date
06/11/2017 19:44
Last modification date
20/08/2019 16:29
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