Hypnotic treatment improves sleep architecture and EEG disruptions and rescues memory deficits in a mouse model of fragile X syndrome.

Autor:	Martinez JD; Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA., Wilson LG; Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA., Brancaleone WP; Undergraduate Program in Neuroscience, University of Michigan, Ann Arbor, MI 48109, USA., Peterson KG; Undergraduate Program in Neuroscience, University of Michigan, Ann Arbor, MI 48109, USA., Popke DS; Undergraduate Program in Neuroscience, University of Michigan, Ann Arbor, MI 48109, USA., Garzon VC; Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA., Perez Tremble RE; Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA., Donnelly MJ; Undergraduate Program in Neuroscience, University of Michigan, Ann Arbor, MI 48109, USA., Mendez Ortega SL; Undergraduate Program in Neuroscience, University of Michigan, Ann Arbor, MI 48109, USA., Torres D; Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA., Shaver JJ; Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA., Jiang S; Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA., Yang Z; Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA., Aton SJ; Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: saton@umich.edu.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2024 Jun 25; Vol. 43 (6), pp. 114266. Date of Electronic Publication: 2024 May 23.
DOI:	10.1016/j.celrep.2024.114266
Abstrakt:	Fragile X syndrome (FXS) is associated with disrupted cognition and sleep abnormalities. Sleep loss negatively impacts cognitive function, and one untested possibility is that disrupted cognition in FXS is exacerbated by abnormal sleep. We tested whether ML297, a hypnotic acting on G-protein-activated inward-rectifying potassium (GIRK) channels, could reverse sleep phenotypes and disrupted memory in Fmr1 -/y mice. Fmr1 -/y mice exhibit reduced non-rapid eye movement (NREM) sleep and fragmented NREM architecture, altered sleep electroencephalogram (EEG) oscillations, and reduced EEG coherence between cortical areas; these are partially reversed following ML297 administration. Treatment following contextual fear or spatial learning restores disrupted memory consolidation in Fmr1 -/y mice. During memory recall, Fmr1 -/y mice show an altered balance of activity among hippocampal principal neurons vs. parvalbumin-expressing interneurons; this is partially reversed by ML297. Because sleep disruption could impact neurophysiological phenotypes in FXS, augmenting sleep may improve disrupted cognition in this disorder. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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