Header

UZH-Logo

Maintenance Infos

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


Holst, Sebastian C; Sousek, Alexandra; Hefti, Katharina; Saberi-Moghadam, Sohrab; Buck, Alfred; Ametamey, Simon M; Scheidegger, Milan; Franken, Paul; Henning, Anke; Seifritz, Erich; Tafti, Mehdi; Landolt, Hans-Peter (2017). Cerebral mGluR5 availability contributes to elevated sleep need and behavioral adjustment after sleep deprivation. eLife, 6:e28751.

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.

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.

Statistics

Citations

Dimensions.ai Metrics
1 citation in Web of Science®
1 citation in Scopus®
2 citations in Microsoft Academic
Google Scholar™

Altmetrics

Downloads

4 downloads since deposited on 12 Feb 2018
4 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Pharmacology and Toxicology
07 Faculty of Science > Institute of Pharmacology and Toxicology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:5 October 2017
Deposited On:12 Feb 2018 20:01
Last Modified:19 Aug 2018 14:18
Publisher:eLife Sciences Publications Ltd.
ISSN:2050-084X
OA Status:Gold
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.7554/eLife.28751
PubMed ID:28980941
Project Information:
  • : FunderSNSF
  • : Grant ID320030_135414
  • : Project TitleGlutamatergic mechanisms in sleep-wake homeostasis in health and disease - molecular brain imaging and pharmacogenetics

Download

Download PDF  'Cerebral mGluR5 availability contributes to elevated sleep need and behavioral adjustment after sleep deprivation'.
Preview
Content: Published Version
Filetype: PDF
Size: 3MB
View at publisher
Licence: Creative Commons: Attribution 4.0 International (CC BY 4.0)