Biomarkers for the two phase switches of mammalian hibernation

哺乳动物冬眠两个阶段转换的生物标志物

• 批准号: 7586799
• 负责人: SANDRA L MARTIN
• 金额: $ 37.57万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-15 至 2012-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7586799
• 关键词: Abbreviations; Animals; Arousal; Biochemical; Biological Markers; Biology; Body Temperature; Body Weight decreased; Brain; Brain Stem; Characteristics; Communities; Development; Drug Delivery Systems; Ensure; Event; Exhibits; Fatty acid glycerol esters; Foundations; Gel; Gene Expression; Genetic; Goals; Growth; Health; Heart; Heart Arrest; Hematological Disease; Hibernation; Homeostasis; Human; Hypothalamic structure; Lead; Liquid Chromatography; Liver; Lung; Mammals; Mass Spectrum Analysis; Medicine; Metabolic; Molecular; Monitor; NMR Spectroscopy; Names; Nature; Operative Surgical Procedures; Organ; Organ Transplantation; Outcome; Pathway interactions; Pattern; Phase; Phenotype; Phylogenetic Analysis; Plasma; Proteins; Proteomics; Protocols documentation; Reperfusion Injury; Reproduction; Research; Resistance; Resources; Sampling; Science; Seasons; Source; Spermophilus; Stroke; Techniques; Telemetry; Testing; Therapeutic Intervention; Tissue Banking; Tissue Banks; Tissue Extracts; Tissues; Trauma; Weight Gain; Work; animal tissue; base; depressed; depression; falls; improved; insight; metabolomics; natural hypothermia; novel; protein metabolite; respiratory; success

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.

冬眠的哺乳动物会降低它们的新陈代谢、心率和呼吸频率，以及它们的核心身体