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转化节律光生物学中的啮齿动物模型。

Rodent models in translational circadian photobiology.

机构信息

Sir Jules Thorn Sleep and Circadian Neuroscience Institute (SCNi), Kavli Institute for NanoScience Discovery, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom.

Sir Jules Thorn Sleep and Circadian Neuroscience Institute (SCNi), Kavli Institute for NanoScience Discovery, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom.

出版信息

Prog Brain Res. 2022;273(1):97-116. doi: 10.1016/bs.pbr.2022.02.015. Epub 2022 Mar 21.

Abstract

Over the last decades remarkable advances have been made in the understanding of the photobiology of circadian rhythms. The identification of a third photoreceptive system in the mammalian eye, in addition to the rods and cones that mediate vision, has transformed our appreciation of the role of light in regulating physiology and behavior. These photosensitive retinal ganglion cells (pRGCs) express the blue-light sensitive photopigment melanopsin and project to the suprachiasmatic nuclei (SCN)-the master circadian pacemaker-as well as many other brain regions. Much of our understanding of the fundamental mechanisms of the pRGCs, and the processes that they regulate, comes from mouse and other rodent models. Here we describe the contribution of rodent models to circadian photobiology, including both their strengths and limitations. In addition, we discuss how an appreciation of both rodent and human data is important for translational circadian photobiology. Such an approach enables a bi-directional flow of information whereby an understanding of basic mechanisms derived from mice can be integrated with studies from humans. Progress in this field is being driven forward at several levels of analysis, not least by the use of personalized light measurements and photoreceptor specific stimuli in human studies, and by studying the impact of environmental, rather than laboratory, lighting on different rodent models.

摘要

在过去的几十年里,人们对生物钟的光生物学有了显著的认识。哺乳动物眼睛中除了介导视觉的视杆细胞和视锥细胞之外,还有第三套感光系统的发现,改变了我们对光调节生理和行为的作用的认识。这些感光视网膜神经节细胞 (pRGCs) 表达对蓝光敏感的视色素黑视蛋白,并投射到视交叉上核 (SCN)——生物钟的主起搏器——以及许多其他脑区。我们对 pRGCs 的基本机制以及它们所调节的过程的理解,很大程度上来自于小鼠和其他啮齿动物模型。在这里,我们描述了啮齿动物模型对生物钟光生物学的贡献,包括它们的优势和局限性。此外,我们还讨论了如何重视啮齿动物和人类的数据对于转化生物钟光生物学的重要性。这种方法可以实现信息的双向流动,即将从老鼠身上获得的基本机制的理解与来自人类的研究相结合。该领域的进展在多个分析层面上得到了推动,不仅是在人类研究中使用个性化的光测量和光感受器特异性刺激,而且还研究了环境光而不是实验室光对不同啮齿动物模型的影响。

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