Mechanisms and neuroanatomical bases of metabolic depression in the Djungarian hamster.

正加仓鼠代谢抑郁的机制和神经解剖学基础。

• 批准号: 399844041
• 负责人: Professorin Dr. Annika Herwig
• 金额: --
• 依托单位: Institut für Neurobiologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2023-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/399844041?language=en
• 关键词: Mechanisms; neuroanatomical; bases; metabolic; depression

Daily torpor is a powerful strategy of Djungarian hamsters to reduce energy expenditure in response to predictable or acute energetic challenges. During torpor, metabolic rate is suppressed by 75% and body temperature drops to ≥ 15°C. Although torpor physiology is well studied in this species, knowledge about regulatory systems and mechanisms is still fragmented. The use of torpor is, directly or indirectly, related to energy shortage, and previous studies have suggested that glucose availability may be involved in its regulation. However, data have remained controversial. Here we want to assess the role of glucose availability in different forms of torpor – spontaneous torpor that occurs in a seasonal context as well as fasting induced torpor that can be used in response to acute food restriction. By using a novel telemetry method, we want to continuously measure serum glucose levels in vivo during torpor episodes, precisely relay it to measurements of metabolic rate and body temperature and thereby identify its role in torpor induction. Analysis of glucose sensing in tanycytes at the blood-brain interface and detailed gene expression studies in the hypothalamus will add important information about transmission to the brain and potential regulatory mechanisms. In a second approach, we aim to gain precise anatomical information about hypothalamic centers involved in torpor induction. Currently, information about active brain centers in torpor is very scarce, although this information is essential to understand the basis of metabolic depression. Here we want to combine anatomical and functional investigations, by using detailed immunohistochemical c-Fos analysis coupled with Illumina sequencing of specifically identified hypothalamic nuclei activated during torpor entrance. Combining state of the art in vivo, neurophysiological, anatomical and molecular methods, this project aims to better understand the mechanisms of metabolic depression in mammals. Disentangling the regulatory mechanisms of torpid states, bears great potential for clinical applications that could greatly benefit from controlling metabolism in humans.

每日麻木是丛林仓鼠的一种强大的策略，以减少能量消耗，以应对可预测的或急性的能量挑战。在昏迷期间，代谢率被抑制了75%，体温下降到≥15°C。尽管这种物种的麻木生理学研究得很好，但关于调节系统和机制的知识仍然支离破碎。昏迷的使用直接或间接地与能源短缺有关，先前的研究表明，葡萄糖的可获得性可能参与了它的调节。然而，数据仍然存在争议。在这里，我们想要评估葡萄糖供应在不同形式的麻木中的作用--发生在季节性背景下的自发性麻木，以及可用于应对急性食物限制的禁食诱发的麻木。通过使用一种新的遥测方法，我们希望在昏迷发作期间连续测量体内的血糖水平，准确地将其传递给代谢率和体温的测量，从而确定其在昏迷诱导中的作用。分析血-脑界面的松弛细胞中的葡萄糖感应和下丘脑的详细基因表达研究，将增加有关向大脑传递和潜在调控机制的重要信息。在第二种方法中，我们的目标是获得有关参与麻木诱导的下丘脑中枢的精确解剖学信息。目前，有关麻木中活跃的大脑中心的信息非常稀少，尽管这些信息对于理解代谢性抑郁的基础是必不可少的。在这里，我们希望结合解剖学和功能研究，通过使用详细的免疫组织化学c-Fos分析结合Illumina测序，对在麻木进入时激活的特定的下丘脑核团进行研究。该项目结合了体内最新技术、神经生理学、解剖学和分子方法，旨在更好地了解哺乳动物代谢抑制的机制。解开迟钝状态的调节机制，具有极大的临床应用潜力，可以极大地受益于控制人类的新陈代谢。