Human apolipoprotein E4 targeted replacement in mice reveals increased susceptibility to sleep disruption and intermittent hypoxia.

American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Navita KaushalD Gozal

Abstract

Intermittent hypoxia (IH) and sleep fragmentation (SF) are major manifestations of sleep apnea, a frequent condition in aging humans. Sleep perturbations are frequent in Alzheimer's disease (AD) and may underlie the progression of disease. We hypothesized that acute short-term IH, SF, and their combination (IH+SF) may reveal unique susceptibility in sleep integrity in a murine model of AD. The effects of acute IH, SF, and IH+SF on sleep architecture, delta power, sleep latency, and core body temperature were assessed in adult male human ApoE4-targeted replacement mice (hApoE4) and wild-type (WT) controls. Slow wave sleep (SWS) was significantly reduced, and rapid eye movement (REM) sleep was almost abolished during acute exposure to IH alone and IH+SF for 6 h in hApoE4, with milder effects in WT controls. Decreased delta power during SWS did not show postexposure rebound in hApoE4 unlike WT controls. IH and IH+SF induced hypothermia, which was more prominent in hApoE4 than WT controls. Mice subjected to SF also showed sleep deficits but without hypothermia. hApoE4 mice, unlike WT controls, exhibited increased sleep propensity, especially following IH and IH+SF, suggesting limited ability for sleep recovery in hApoE4 mice. These...Continue Reading

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Citations

Dec 3, 2014·Neuroscience and Biobehavioral Reviews·Weihong Pan, Abba J Kastin
Mar 5, 2016·Nature Reviews. Endocrinology·Alex Gileles-HillelDavid Gozal
Oct 9, 2015·Sleep Medicine Reviews·David GozalF Javier Nieto
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May 23, 2014·Sleep Medicine Reviews·Laure Peter-DerexBernard Croisile
Jul 4, 2020·Journal of Sleep Research·Gabriel Natan PiresMonica Levy Andersen
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Dec 20, 2019·Therapeutic Advances in Respiratory Disease·Abdelnaby KhalyfaDavid Gozal
Nov 30, 2019·Sleep·Carolina Cubillos-ZapataFrancisco García-Rio
Sep 12, 2020·Sleep Medicine·S M RomanellaE Santarnecchi
Apr 17, 2021·Ageing Research Reviews·Johannes BurtscherGrégoire P Millet
Aug 31, 2021·American Journal of Physiology. Endocrinology and Metabolism·Sarah N Framnes-DeBoerDeanna M Arble

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