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在过表达钙/钙调蛋白依赖性蛋白激酶IV的老年雄性小鼠中，睡眠得到改善。

Sleep is enhanced in aged male mice that overexpress calcium/calmodulin-dependent protein kinase IV.

作者信息

Feeney Sierra P, Threlfall Erin, Bilboa James M, Angelakos Christopher C, Wimmer Mathieu E, Kida Satoshi, Abel Ted, Tudor Jennifer C

机构信息

Department of Biology, Saint Joseph's University, Philadelphia, PA, United States.

Department of Biology, University of Pennsylvania, Philadelphia, PA, United States.

出版信息

Front Neurosci. 2025 Jun 3;19:1596602. doi: 10.3389/fnins.2025.1596602. eCollection 2025.

DOI:10.3389/fnins.2025.1596602
PMID:40529249
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12170523/
Abstract

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 (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 calcium/calmodulin-dependent protein kinase IV (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.

摘要

衰老过程中出现的睡眠-觉醒模式失调已有充分记录，且与调节睡眠的细胞内信号通路变化相一致，如钙/钙调蛋白依赖性蛋白激酶（CaMKII）/环磷酸腺苷反应元件结合蛋白（CREB）通路。然而，对于CaMK家族其他激活CREB的成员，如钙/钙调蛋白依赖性蛋白激酶IV（CaMKIV）与睡眠调节之间的关系，我们了解得要少得多。使用2至4个月大（年轻成年）和22至24个月大（老龄）的雄性和雌性CaMKIV过表达（CaMKIV-OE）小鼠，我们观察到，与年龄和性别匹配的对照相比，老龄雄性小鼠前脑中CaMKIV的过表达减少了清醒时间，增加了非快速眼动（NREM）睡眠和快速眼动（REM）睡眠的时长，但年轻成年雄性小鼠没有这种现象。相反，过表达CaMKIV的雌性小鼠与野生型对照相比，无论年龄大小，在每种警觉状态下所花时间的百分比均无显著差异。虽然CaMKIV过表达也导致年轻成年和老龄雄性小鼠睡眠-觉醒碎片化增加，但老龄雌性小鼠的NREM睡眠更稳定。总体而言，我们的结果表明，CaMKIV过表达可增强老龄雄性小鼠的睡眠，并根据性别和年龄对睡眠-觉醒结构产生不同影响，为CaMKIV过表达增强记忆的潜在机制提供了见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65a0/12170523/23a4e904105d/fnins-19-1596602-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65a0/12170523/fa9df94b0b26/fnins-19-1596602-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65a0/12170523/e50d56ca670f/fnins-19-1596602-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65a0/12170523/5119249ffe07/fnins-19-1596602-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65a0/12170523/5735b5700a79/fnins-19-1596602-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65a0/12170523/cc4f91f12b76/fnins-19-1596602-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65a0/12170523/8c9833ba535e/fnins-19-1596602-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65a0/12170523/45605b5e1aa9/fnins-19-1596602-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65a0/12170523/23a4e904105d/fnins-19-1596602-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65a0/12170523/fa9df94b0b26/fnins-19-1596602-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65a0/12170523/e50d56ca670f/fnins-19-1596602-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65a0/12170523/5119249ffe07/fnins-19-1596602-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65a0/12170523/5735b5700a79/fnins-19-1596602-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65a0/12170523/cc4f91f12b76/fnins-19-1596602-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65a0/12170523/8c9833ba535e/fnins-19-1596602-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65a0/12170523/45605b5e1aa9/fnins-19-1596602-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65a0/12170523/23a4e904105d/fnins-19-1596602-g008.jpg

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