Biomarkers for the two phase switches of mammalian hibernation

冬眠的哺乳动物会抑制它们的新陈代谢、心脏和呼吸频率，以及它们的核心身体 温度(TB)，以进入一种称为麻木的状态。在像地松鼠这样的冬眠动物中，麻木恰恰是 仅使用内生机制进行控制和完全可逆，但对 作为冬眠关键转变基础的分子事件。对生物化学方面的理解 足以在非冬眠者中概括它们对人类健康的深远影响，提供了一种 前所未有的机会，以改善心脏骤停、中风、创伤和 体温过低，以及器官移植和常规手术。冬眠是一种自适应策略 被许多远亲哺乳动物利用的能量守恒；这一广泛的系统发育分布 有力地论证了表型背后的遗传能力在哺乳动物中是共享的。因此，我们预测 对哺乳动物自然冬眠的理解将导致SAFE的合理发展 人类应用的低代谢和保护策略。在这里，我们提出冬眠包括 两个生化开关：第一个开关是夏季到冬季的开关，它重置了植物体内的基因表达 通向受保护表型的途径数。第二个开关是麻木到觉醒的开关， 创造冬眠表型特有的异温模式，并负责可逆 代谢抑制。与这两个开关相关的标记将使用蛋白质组学和 代谢组学技术。这项工作的成功关键取决于仔细收集的一组样本 基于与这两个开关相关联的自然节奏。来自13层地面的21个样本组 将对松鼠进行分析，其中9只松鼠的夏季到冬季的转换和12只松鼠的麻木到觉醒的转换。首字母 重点将放在血浆、心脏、肺、肝脏和大脑上，但将收集其他组织来建立组织库 这些宝贵的时间点为进一步的研究和冬眠研究社区所用。 这些标记的识别增加了对哺乳动物冬眠的了解，并提供了重要的 对实现代谢抑制和保护的自然机制的新见解 哺乳动物的缺血/再灌注损伤。这些标记为发现新目标提供了一个尚未开发的来源 用于人类心肺和血液疾病的治疗干预。

Mammals that hibernate depress their metabolic, heart and respiratory rates, as well as their core body temperature (Tb) to enter a state called torpor. In hibernators such as ground squirrels, torpor is precisely controlled and fully reversible using only endogenous mechanisms, yet relatively little is known about the molecular events that underlie hibernation's critical transitions. Understanding the biochemical aspects well enough to recapitulate them in a non-hibernator has profound implications for human health, offering an unprecedented opportunity to improve outcomes for victims of cardiac arrest, stroke, trauma, and hypothermia, as well as in organ transplant and routine surgery. Hibernation is an adaptive strategy for energy conservation that is exploited by many distantly related mammals; this broad phylogenetic distribution argues strongly that genetic capability underlying the phenotype is shared among mammals. Thus, we predict that an understanding of natural mammalian hibernation will lead to rational development of safe hypometabolic and protective strategies for human applications. Here we propose that hibernation comprises two biochemical switches: the first switch is a summer-to-winter switch that resets gene expression in a number of pathways leading to a protected phenotype. The second switch is a torpor-to-arousal switch that creates the heterothermic pattern characteristic to the hibernating phenotype and is responsible for reversible metabolic suppression. Markers associated with these two switches will be identified using proteomic and metabolomic techniques. The success of this work critically depends upon a carefully collected set of samples based upon the natural rhythms associated with the two switches. 21 sample groups from 13-lined ground squirrels will be analyzed, 9 for the summer-to-winter switch and 12 for the torpor-to-arousal switch. Initial focus will be on plasma, heart, lung, liver and brain, but other tissues will be collected to make a tissue bank of these valuable timepoints for additional studies and for use by the hibernation research community. Identification of these markers increases understanding of mammalian hibernation, and provides significant novel insights into natural mechanisms that achieve metabolic suppression and protection from ischemia/reperfusion injury in mammals. These markers offer an untapped source for discovery of new targets for therapeutic intervention in heart, lung and blood diseases in humans.