ORIGINAL RESEARCH article
Front. Neurosci.
Sec. Sleep and Circadian Rhythms
Volume 19 - 2025 | doi: 10.3389/fnins.2025.1596602
This article is part of the Research TopicCircadian Rhythms and AgingView all articles
Sleep is enhanced in aged male mice that overexpress calcium/calmodulin-dependent protein kinase IV
Provisionally accepted
Sierra P Feeney1
Erin Threlfall1
James M Bilboa1Christopher C Angelakos2Mathieu E Wimmer3
Satoshi Kida4
Ted Abel5
Jennifer Choi Tudor1*- 1Saint Joseph's University, Philadelphia, United States
- 2University of Pennsylvania, Philadelphia, Pennsylvania, United States
- 3Temple University, Philadelphia, Pennsylvania, United States
- 4Tokyo University of Agriculture, Tokyo, Tokyo, Japan
- 5The University of Iowa, Iowa City, Iowa, United States
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
The dysregulation of sleep-wake patterns that occurs during aging is well documented and coincides with changes in intracellular signaling pathways that regulate sleep, such as the calcium/calmodulin-dependent protein kinase (CaMK) II (CaMKII)/cyclic-AMP response element-binding protein (CREB) pathway. However, much less is known about the relationship between other CREB-activating members of the CaMK family, such as CaMKIV, and the regulation of sleep. Using 2-to 4-month-old (young adult) and 22-to 24-month-old (aged) male and female CaMKIV-overexpressing (CaMKIV-OE) mice, we observed that overexpression of CaMKIV in the forebrain decreased wakefulness and increased the amount of non-rapid eye movement (NREM) and rapid eye movement (REM) sleep in aged male mice, but not young adult male mice, in comparison to age-and sex-matched controls.Conversely, female mice overexpressing CaMKIV displayed no significant differences in the percentage of time spent in each vigilance state compared to their wild-type counterparts, regardless of age. While CaMKIV overexpression also led to more sleep-wake fragmentation in young adult and aged male mice, aged female mice displayed more consolidated NREM sleep. Overall, our results suggest that CaMKIV overexpression enhances sleep in aged male mice, and differentially affects sleep-wake architecture based on sex and age, providing insights into the potential mechanism by which CaMKIV overexpression enhances memory.
Keywords: Aging, Circadian rhythms and sleep, cyclic-AMP response element binding protein, Electroencephalography, Memory Word Count: ~7, 000 Figure Count: 8 + 2 Supplemental
Received: 19 Mar 2025; Accepted: 05 May 2025.
Copyright: © 2025 Feeney, Threlfall, Bilboa, Angelakos, Wimmer, Kida, Abel and Tudor. 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: Jennifer Choi Tudor, Saint Joseph's University, Philadelphia, United States
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.