The regulation of circadian and ultradian rhythmicity of circulating glucocorticoid hormones and their role in the optimisation of limbic activity

循环糖皮质激素的昼夜节律和超昼夜节律的调节及其在优化边缘活动中的作用

• 批准号: BB/G00403X/1
• 负责人: Stafford Lightman
• 金额: $ 75.92万
• 依托单位: University of Bristol
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2009
• 资助国家: 英国
• 起止时间: 2009 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FG00403X%2F1
• 关键词: regulation; circadian; ultradian; rhythmicity; circulating

Biological rhythms are critical for good health and the optimal function of many physiological systems. The daily-circadian-regulation of body rhythms is controlled by a group of cells in the suprachiasmatic nucleus (SCN) of the hypothalamus. These cells employ a specific molecular machinery of so-called clock genes, which use a self-regulating feedback system to maintain an approximate 24-hour rhythm of activity. This central clock / whose activity is fine tuned by external cues such as light / regulates multiple physiological systems including endocrine, metabolic, cardiovascular, cognitive and behavioural outputs. The discovery that clock genes are also found in other areas of the brain and in many peripheral tissues challenges the concept of a single SCN pacemaker. Unlike the SCN however, the clock genes in these other areas do not necessarily express independent long-term rhythms and need the SCN to entrain and maintain their rhythms. This immediately demands that we address the question of how the SCN can control these slave oscillators. One obvious candidate as a controller of the clock genes outside the SCN is the glucocorticoid secreted by the adrenal cortex, which is secreted in a circadian rhythm. This rhythm is under the control of the SCN, and we have recently shown that signalling through this system depends on both its circadian rhythm and the pulse character of its secretion. Furthermore, we know that a critically important clock gene / period 1 (per 1) / has the molecular signature that allows it to be regulated by glucocorticoids. In this application therefore, we want to define how the SCN effects glucocorticoid secretory dynamics, and how changes in these dynamics alter the regulation of clock genes in areas of the brain vital for cognitive function and anxiety behaviour. We shall then go on to investigate how these changes in clock genes alter the efficiency of neurones to interact (synaptic plasticity) and how this in turn alters the memory abilities of conscious animals.

生物节律对于身体健康和许多生理系统的最佳功能至关重要。下丘脑视交叉上核（SCN）中的一组细胞控制着身体节律的昼夜节律调节。这些细胞使用所谓的时钟基因的特定分子机制，其使用自我调节反馈系统来维持大约24小时的活动节奏。这种中央时钟/其活动由外部线索（例如光）微调/调节多个生理系统，包括内分泌、代谢、心血管、认知和行为输出。在大脑的其他区域和许多外周组织中也发现了时钟基因，这一发现对单一SCN起搏器的概念提出了挑战。然而，与SCN不同的是，这些其他区域中的时钟基因不一定表达独立的长期节律，而是需要SCN来引导和维持它们的节律。这立即要求我们解决SCN如何控制这些从振荡器的问题。作为SCN外的时钟基因控制器的一个明显的候选者是肾上腺皮质分泌的糖皮质激素，其以昼夜节律分泌。这种节律受到SCN的控制，我们最近表明，通过该系统的信号传递取决于其昼夜节律和分泌物的脉冲特征。此外，我们知道一个非常重要的时钟基因/周期1（每1）/具有允许它被糖皮质激素调节的分子特征。因此，在本申请中，我们希望定义SCN如何影响糖皮质激素分泌动力学，以及这些动力学的变化如何改变对认知功能和焦虑行为至关重要的大脑区域中的时钟基因的调节。然后，我们将继续研究生物钟基因的这些变化如何改变神经元相互作用的效率（突触可塑性），以及这又如何改变有意识动物的记忆能力。

项目成果

Ultradian corticosterone secretion is maintained in the absence of circadian cues.

在没有昼夜节律提示的情况下，超昼夜皮质酮分泌得以维持。

• DOI: 10.1111/j.1460-9568.2012.08213.x
• 发表时间: 2012
• 期刊: The European journal of neuroscience
• 作者: Waite EJ

Acute stress causes rapid synaptic insertion of Ca2+ -permeable AMPA receptors to facilitate long-term potentiation in the hippocampus.

急性应激会导致CA2+可渗透AMPA受体的快速突触插入，以促进海马的长期增强。

• DOI: 10.1093/brain/awt293
• 发表时间: 2013-12
• 期刊: Brain : a journal of neurology
• 作者: Whitehead G;Jo J;Hogg EL;Piers T;Kim DH;Seaton G;Seok H;Bru-Mercier G;Son GH;Regan P;Hildebrandt L;Waite E;Kim BC;Kerrigan TL;Kim K;Whitcomb DJ;Collingridge GL;Lightman SL;Cho K
• 通讯作者: Cho K