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

日常冬眠是保加利亚仓鼠在应对可预测或急性能量挑战时减少能量消耗的有力策略。冬眠时，代谢率被抑制75%，体温下降至≥15℃。虽然冬眠生理学在这个物种中得到了很好的研究，但关于调节系统和机制的知识仍然是碎片化的。冬眠的使用直接或间接地与能量短缺有关，以前的研究表明葡萄糖可用性可能参与其调节。然而，数据仍然存在争议。在这里，我们想要评估葡萄糖可用性在不同形式的冬眠中的作用——在季节背景下发生的自发性冬眠，以及可用于应对急性食物限制的禁食性冬眠。通过使用一种新颖的遥测方法，我们希望在冬眠期间连续测量体内的血清葡萄糖水平，并将其精确地传递到代谢率和体温的测量中，从而确定其在冬眠诱导中的作用。分析血脑界面上伸长细胞的葡萄糖感知和下丘脑中详细的基因表达研究将为传递到大脑和潜在的调节机制提供重要信息。在第二种方法中，我们的目标是获得参与麻木诱导的下丘脑中心的精确解剖信息。虽然这些信息对于理解代谢性抑郁症的基础是必不可少的，但是目前关于睡眠状态下活跃的大脑中枢的信息非常少。在这里，我们想结合解剖和功能研究，通过使用详细的免疫组织化学c-Fos分析，结合Illumina测序特异性鉴定的下丘脑核在冬眠进入时激活。本项目旨在结合体内、神经生理学、解剖学和分子生物学等多种方法，更好地了解哺乳动物代谢抑制的机制。阐明休眠状态的调控机制，具有巨大的临床应用潜力，可以极大地受益于控制人类的代谢。

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.