昼夜节律和褪黑激素研究中的小鼠模型。

IF 8.3 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Journal of Pineal Research Pub Date : 2024-07-04 DOI:10.1111/jpi.12986
Horst-Werner Korf, Charlotte von Gall
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引用次数: 0

摘要

这篇论文回顾了近交系和转基因小鼠品系在破译哺乳动物褪黑激素能和昼夜节律系统方面的作用。它重点研究了作为褪黑激素工厂的松果体器官以及褪黑激素能系统的两个主要靶点--上丘脑核(SCN)和下丘脑旁(PT)。哺乳动物的松果体细胞与真正的松果体和视网膜感光细胞具有相同的分子特征,每晚合成并分泌褪黑激素到血液和脑脊液中。值得注意的是,深部松果体细胞与视网膜/网膜区域之间存在神经元样连接,这表明松果体与大脑之间存在直接交流。啮齿类动物褪黑激素生物合成的控制涉及转录调控,包括 CREB 磷酸化和 mPer1 的上调。在SCN中,褪黑激素作用于MT1和MT2受体。褪黑激素并不是维持 SCN 分子时钟节律所必需的,但它对光对昼夜节律的同步有明显的影响,通过作用于 MT2 受体,促进昼夜节律系统重新适应 SCN 分子时钟水平的相位变化,并在昼夜节律系统中发挥稳定作用,运动活动记录证明了这一点。虽然褪黑激素对 SCN 的影响是微妙的,但它对 PT 功能至关重要。它通过 MT1 受体驱动昼夜节律内在分子时钟以及控制季节节律的逆行和顺行输出途径。虽然近亲繁殖和转基因小鼠不表现出季节性繁殖,但如果动物缺乏褪黑激素,来自PT的通路则完全完好无损。因此,只有富含褪黑激素的品系才适合研究昼夜节律和褪黑激素能系统。
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Mouse Models in Circadian Rhythm and Melatonin Research

This contribution reviews the role of inbred and transgenic mouse strains for deciphering the mammalian melatoninergic and circadian system. It focusses on the pineal organ as melatonin factory and two major targets of the melatoninergic system, the suprachiasmatic nuclei (SCN) and the hypophysial pars tuberalis (PT). Mammalian pinealocytes sharing molecular characteristics with true pineal and retinal photoreceptors synthesize and secrete melatonin into the blood and cerebrospinal fluid night by night. Notably, neuron-like connections exist between the deep pinealocytes and the habenular/pretectal region suggesting direct pineal-brain communication. Control of melatonin biosynthesis in rodents involves transcriptional regulation including phosphorylation of CREB and upregulation of mPer1. In the SCN, melatonin acts upon MT1 and MT2 receptors. Melatonin is not necessary to maintain the rhythm of the SCN molecular clockwork, but it has distinct effects on the synchronization of the circadian rhythm by light, facilitates re-entrainment of the circadian system to phase advances in the level of the SCN molecular clockwork by acting upon MT2 receptors and plays a stabilizing role in the circadian system as evidenced from locomotor activity recordings. While the effects in the SCN are subtle, melatonin is essential for PT functions. Via the MT1 receptor it drives the PT-intrinsic molecular clockwork and the retrograde and anterograde output pathways controlling seasonal rhythmicity. Although inbred and transgenic mice do not show seasonal reproduction, the pathways from the PT are fully intact if the animals are melatonin proficient. Thus, only melatonin-proficient strains are suited to investigate the circadian and melatoninergic systems.

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来源期刊
Journal of Pineal Research
Journal of Pineal Research 医学-内分泌学与代谢
CiteScore
17.70
自引率
4.90%
发文量
66
审稿时长
1 months
期刊介绍: The Journal of Pineal Research welcomes original scientific research on the pineal gland and melatonin in vertebrates, as well as the biological functions of melatonin in non-vertebrates, plants, and microorganisms. Criteria for publication include scientific importance, novelty, timeliness, and clarity of presentation. The journal considers experimental data that challenge current thinking and welcomes case reports contributing to understanding the pineal gland and melatonin research. Its aim is to serve researchers in all disciplines related to the pineal gland and melatonin.
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