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使用啮齿动物模型对化疗引起的昼夜节律紊乱的机制性见解。

Mechanistic insights into chemotherapy-induced circadian disruption using rodent models.

作者信息

Tapp Zoe M, Ghosh Amiya K, Obrietan Karl H, Pyter Leah M

机构信息

Institute for Behavioral Medicine Research, The Ohio State University, Columbus, OH, USA.

Department of Neuroscience, The Ohio State University, Columbus, OH, USA.

出版信息

Trends Neurosci. 2025 Apr;48(4):283-296. doi: 10.1016/j.tins.2024.12.011. Epub 2025 Jan 22.

Abstract

Chemotherapy treatment can significantly increase the survival of patients with cancer, but it also causes collateral damage in the body that can lead to treatment dose reductions and can reduce patient quality of life. One understudied side effect of chemotherapy is circadian disruption, which is associated with lasting biological and behavioral toxicities. Mechanisms of how chemotherapy alters circadian rhythms remain largely unknown, although leveraging rodent models may provide insights into causes and consequences of this disruption. Here, we review physiological, molecular, and behavioral evidence of central and peripheral circadian disruption in various rodent models of chemotherapy and discuss possible mechanisms driving these circadian disruptions. Overall, restoring circadian rhythms following treatment-induced disruptions may be a novel target by which to improve the health and quality of life of survivors.

摘要

化疗能够显著提高癌症患者的生存率,但它也会对身体造成附带损害,这可能导致治疗剂量减少,并会降低患者的生活质量。化疗一个尚未得到充分研究的副作用是昼夜节律紊乱,它与持久的生物学和行为毒性有关。尽管利用啮齿动物模型可能有助于深入了解这种紊乱的原因和后果,但化疗如何改变昼夜节律的机制在很大程度上仍不清楚。在这里,我们回顾了各种化疗啮齿动物模型中中枢和外周昼夜节律紊乱的生理、分子和行为证据,并讨论了导致这些昼夜节律紊乱的可能机制。总体而言,在治疗引起的紊乱后恢复昼夜节律可能是改善幸存者健康和生活质量的一个新靶点。

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