Gebru Niat T, Beaulieu-Abdelahad David, Gulick Danielle, Blair Laura J
Byrd Alzheimer's Center and Research Institute, Tampa, FL 33613, USA; Department of Molecular Medicine, University of South Florida, Tampa, FL 33612, USA.
Byrd Alzheimer's Center and Research Institute, Tampa, FL 33613, USA; Department of Molecular Medicine, University of South Florida, Tampa, FL 33612, USA.
Cell Stress Chaperones. 2025 Feb;30(1):22-32. doi: 10.1016/j.cstres.2024.12.003. Epub 2024 Dec 12.
Circadian rhythm disruptions have been associated with a wide range of health issues and complications, including an increased risk of circadian rhythm sleep disorders (CRSDs). CRSDs are common among individuals who have been through a traumatic event, particularly in those who have post-traumatic stress disorder (PTSD). Allelic variations in the gene encoding for FK506-binding protein 51 (FKBP51) can increase the susceptibility for PTSD and other stress-related disorders following trauma. At least one of these variants increases the levels of FKBP51 following stress through a glucocorticoid receptor-mediated process. Here, we used a mouse model that overexpresses human FKBP51 throughout the forebrain, rTgFKBP5, to investigate if elevated FKBP51 contributes to circadian rhythm disruption. Surprisingly, our findings indicate a greater rhythm amplitude and decreased rhythm fragmentation in rTgFKBP5 mice, particularly females, compared to controls. Female rTgFKBP5 mice also showed higher corticosterone levels basally and following stress exposure. Overall, this study associates FKBP51 overexpression with beneficial circadian rhythm outcomes.
昼夜节律紊乱与一系列健康问题和并发症有关，包括昼夜节律睡眠障碍（CRSDs）风险增加。CRSDs在经历过创伤性事件的个体中很常见，尤其是那些患有创伤后应激障碍（PTSD）的人。编码FK506结合蛋白51（FKBP51）的基因中的等位基因变异会增加创伤后患PTSD和其他应激相关障碍的易感性。这些变异中至少有一种通过糖皮质激素受体介导的过程在应激后增加FKBP51的水平。在这里，我们使用了一种在整个前脑过表达人FKBP51的小鼠模型rTgFKBP5，来研究升高的FKBP51是否导致昼夜节律紊乱。令人惊讶的是，我们的研究结果表明，与对照组相比，rTgFKBP5小鼠，尤其是雌性小鼠，具有更大的节律振幅和更低的节律碎片化程度。雌性rTgFKBP5小鼠在基础状态和应激暴露后也表现出更高的皮质酮水平。总体而言，这项研究将FKBP51的过表达与有益的昼夜节律结果联系起来。
