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ORIGINAL RESEARCH article

Front. Neurol.
Sec. Neurogenetics
Volume 15 - 2024 | doi: 10.3389/fneur.2024.1430989
This article is part of the Research Topic The Neurogenetics of Circadian Rhythms: Implications for Health and Disease View all 4 articles

The impacts of sex and the 5xFAD model of Alzheimer's disease on the sleep and spatial learning responses to feeding time

Provisionally accepted
Katrina J. Campbell Katrina J. Campbell 1*Peng Jiang Peng Jiang 1,2Christopher Olker Christopher Olker 1Xuanyi Lin Xuanyi Lin 1Sarah Y. Kim Sarah Y. Kim 1Christopher J. Lee Christopher J. Lee 1Eun Joo Song Eun Joo Song 1Fred Turek Fred Turek 1Martha H. Vitaterna Martha H. Vitaterna 1*
  • 1 Northwestern University, Evanston, United States
  • 2 Informatics and Predictive Sciences, Bristol Myers Squibb, Cambridge, United States

The final, formatted version of the article will be published soon.

    The relationships between the feeding rhythm, sleep and cognition in Alzheimer's disease (AD) are incompletely understood, but meal time could provide an easy-to-implement method of curtailing disease-associated disruptions in sleep and cognition. Furthermore, known sex differences in AD incidence could relate to sex differences in circadian rhythm/sleep/cognition interactions.The 5xFAD transgenic mouse model of AD and non-transgenic wild-type controls were studied. Both female and male mice were used. Food access was restricted each day to either the 12-hr light phase (light-fed groups) or the 12-hr dark phase (dark-fed groups). Sleep (electroencephalographic/electromyographic) recording and cognitive behavior measures were collected.The 5xFAD genotype reduces NREM and REM as well as the number of sleep spindles. In wild-type mice, light-fed groups had disrupted vigilance state amounts, characteristics, and rhythms relative to dark-fed groups. These feeding time differences were reduced in 5xFAD mice. Sex modulates these effects. 5xFAD mice display poorer spatial memory that, in female mice, is curtailed by dark phase feeding. Similarly, female 5xFAD mice have decreased anxietyassociated behavior. These emotional and cognitive measures are correlated with REM amount.Discussion: Our study demonstrates that the timing of feeding can alter many aspects of wake, NREM and REM. Unexpectedly, 5xFAD mice are less sensitive to these feeding time effects. 5xFAD mice demonstrate deficits in cognition which are correlated with REM, suggesting that this circadian-timed aspect of sleep may link feeding time and cognition. Sex plays an important role in regulating the impact of feeding time on sleep and cognition in both wild-type and 5xFAD mice, with females showing a greater cognitive response to feeding time than males.

    Keywords: Alzheimer's disease, time-restricted feeding, phase-restricted feeding, Sleep, Cognition, 5xFAD

    Received: 10 May 2024; Accepted: 16 Jul 2024.

    Copyright: © 2024 Campbell, Jiang, Olker, Lin, Kim, Lee, Song, Turek and Vitaterna. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Katrina J. Campbell, Northwestern University, Evanston, United States
    Martha H. Vitaterna, Northwestern University, Evanston, United States

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