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

Holst, S., Sousek, A., Hefti, K., Saberi-Moghadam, S., Buck, A., Ametamey, S., et al. (2017). Cerebral mGluR5 availability contributes to elevated sleep need and behavioral adjustment after sleep deprivation. eLife, 2017(6), 1-23. doi:10.7554/eLife.28751.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0000-C29A-7 Version Permalink: http://hdl.handle.net/21.11116/0000-0001-8577-3
Genre: Journal Article

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Holst, SC, Author
Sousek, A, Author
Hefti, K, Author
Saberi-Moghadam, S, Author
Buck, A, Author
Ametamey, SM, Author
Scheidegger, M, Author
Franken, P, Author
Henning, A1, 2, Author              
Seifritz, E, Author
Tafti, M, Author
Landholt, HP, Author
Affiliations:
1Max Planck Institute for Biological Cybernetics, Max Planck Society, ou_1497794              
2Research Group MR Spectroscopy and Ultra-High Field Methodology, Max Planck Institute for Biological Cybernetics, Max Planck Society, ou_2528692              

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 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.

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 Dates: 2017-10
 Publication Status: Published online
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 Identifiers: DOI: 10.7554/eLife.28751
eDoc: e28751
BibTex Citekey: HolstSHSBASFHSTL2017
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Title: eLife
Source Genre: Journal
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Pages: - Volume / Issue: 2017 (6) Sequence Number: - Start / End Page: 1 - 23 Identifier: -