Aquaporin 4 deletion exacerbates brain impairments in a mouse model of chronic sleep disruption.

CNS Neuroscience & Therapeutics
Rui ZhangMing Xiao

Abstract

As a normal physiological process, sleep has recently been shown to facilitate clearance of macromolecular metabolic wastes from the brain via the glymphatic system. The aim of the present study was to investigate pathophysiological roles of astroglial aquaporin 4 (AQP4), a functional regulator of glymphatic clearance, in a mouse model of chronic sleep disruption (SD). Adult AQP4 null mice and wild-type (WT) mice were given 7 days of SD using the improved rotating rod method, and then received behavioral, neuropathological, and neurochemical analyses. Aquaporin 4 deletion resulted in an impairment of glymphatic transport and accumulation of β-amyloid and Tau proteins in the brain following SD. AQP4 null SD mice exhibited severe activation of microglia, neuroinflammation, and synaptic protein loss in the hippocampus, as well as decreased working memory, compared with WT-SD mice. These results demonstrate that AQP4-mediated glymphatic clearance ameliorates brain impairments caused by abnormal accumulation of metabolic wastes following chronic SD, thus serving as a potential target for sleep-related disorders.

References

Nov 1, 2006·Molecular and Cellular Neurosciences·Xiao-Ning ZengGang Hu
Nov 24, 2006·Proceedings of the National Academy of Sciences of the United States of America·Xiulian SunWeihong Song
May 23, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Xiaoming YaoGeoffrey T Manley
Oct 28, 2008·Journal of Neuroscience Research·Xuechao FengTonghui Ma
Feb 28, 2009·Proceedings of the National Academy of Sciences of the United States of America·Deepak R ThakkerLisa L Shafer
Sep 26, 2009·Science·Jae-Eun KangDavid M Holtzman
Dec 15, 2010·Science·Kwasi G MawuenyegaRandall J Bateman
Jan 25, 2011·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Lihua LiA S Verkman
Feb 19, 2011·The International Journal of Neuropsychopharmacology·Chia-Hsiung ChenWeihong Song
Nov 29, 2011·Experimental Brain Research·Johannes ProxPaul Saftig
Mar 1, 2012·Molecular and Cellular Neurosciences·Wei YangGang Hu
Sep 14, 2013·Current Biology : CB·Ted AbelMatthew P Walker
Oct 19, 2013·Science·Lulu XieMaiken Nedergaard
Nov 23, 2013·Nature Protocols·Marianne LegerThomas Freret
Dec 25, 2013·Clinical & Developmental Immunology·Gabriela Hurtado-AlvaradoBeatriz Gómez-González
Feb 11, 2014·European Journal of Applied Physiology·Andrew ThompsonGreg Atkinson
Jul 22, 2014·Neurobiology of Learning and Memory·Andrew W VargaEric Klann
Sep 11, 2014·Annals of Neurology·Benjamin T KressMaiken Nedergaard
Dec 5, 2014·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Jeffrey J IliffMaiken Nedergaard
Jan 16, 2015·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Benjamin A PlogMaiken Nedergaard
May 8, 2015·Neurochemical Research·Nadia Aalling JessenMaiken Nedergaard
May 29, 2016·Neurobiology of Disease·Weiguo PengRashid Deane
Jul 12, 2016·Neuroscience and Biobehavioral Reviews·Eleonora TobaldiniNicola Montano
Nov 26, 2016·Science·Erik S Musiek, David M Holtzman
Dec 10, 2016·Molecular Neurodegeneration·Thiyagaragan M AchariyarRashid Deane
Feb 28, 2017·Journal of Clinical Psychology in Medical Settings·Daphne Koinis-MitchellAlexander N Ortega
May 26, 2017·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Michele BellesiChiara Cirelli
May 30, 2017·Brain Structure & Function·Shirin KatooziMahmood Amiry-Moghaddam
Jul 20, 2017·Nature Immunology·Inna S AfoninaRudi Beyaert
Jul 30, 2017·Neuropathology and Applied Neurobiology·G G KovacsJ Q Trojanowski
Dec 2, 2017·Annual Review of Pathology·Benjamin A Plog, Maiken Nedergaard
Feb 27, 2018·Translational Psychiatry·Stephanie R Rainey-SmithUNKNOWN AIBL Research Group

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Citations

Dec 29, 2020·Neurochemistry International·Samuel DeurveilherKazue Semba
Jan 20, 2021·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Tekla Maria KylkilahtiIben Lundgaard

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Methods Mentioned

BETA
gene knockout
ELISA

Software Mentioned

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Mouse Home Cage Scan
ImageQuant LAS 4000
ImageJ

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