Neural and cellular basis of fluid homeostasis during hibernation

冬眠期间体液稳态的神经和细胞基础

• 批准号: 2015622
• 负责人: Elena Gracheva
• 金额: $ 140万
• 依托单位: Yale University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-15 至 2024-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2015622&HistoricalAwards=false
• 关键词: Neural; cellular; basis; fluid; homeostasis

Mammalian hibernation is fascinating. During a short period of time, hibernating animals undergo dramatic adaptive changes, including reduction in heart and respiration rate and decrease of core body temperature from 37°C (98.6°F) to 4°C (39°F), yet they do not experience cold-induced pain, and their organs continue to function despite being cold, non-functional, and deprived of oxygen for eight months out of the year. Moreover, during hibernation, animals do not drink; therefore, hibernators must rely solely on the management and utilization of internal resources for long-term survival. This project seeks to understand the molecular mechanisms that allows hibernators to survive for months without water, using a range of cutting-edge tools and approaches not been previously used for hibernation research, such as optogenetics and fiber photometry. The outcomes of this study will have broad scientific implications, including a better understanding of general mechanisms that regulate internal water and ionic balance common to all mammals. This project also involves educational and outreach efforts in the context of an extracurricular educational program (Sensory Physiology Club) that promotes scientific knowledge in human and animal physiology among school students from middle- and high schools from Connecticut, New York, and Massachusetts. The efforts are designed to spark interest in biological science through lectures and interactive experimental activities that go beyond the science curricula of most schools.The main scientific goal of this study is to broaden our limited understanding of fluid homeostasis in mammals at the cellular, molecular, and circuit levels by studying ground squirrels during hibernation. This project tests the hypothesis that ground squirrels endure long-term water deprivation in part by modifying the hypothalamic axis, which controls thirst and mediates the release of antidiuretic hormones. Specific aims of this proposal include investigation of the neuronal mechanisms that support the release of vasopressin and oxytocin from the posterior pituitary, and suppress water-seeking behavior during hibernation. This project combines cellular, molecular, and organismal levels of research and uses tools and approaches from a spectrum of disciplines: state-specific biochemical analysis of neuropeptides and hormones, quantitative analysis of hormonal production, differential transcriptomics, electron microscopic and morphometric analyses of hormonal release, and behavioral analyses of drinking behavior. A major innovative aspect of this project is the use of optogenetics, fiber photometry, and electrophysiological tools, which have not been used previously with hibernating animals. The outcomes of this study will delineate general principles of fluid-ionic balance fine-tuning, suggest a strategy to sustain life when water is unavailable, and predict whether hibernation can be induced in other mammals.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

哺乳动物的冬眠是令人着迷的，在短时间内，冬眠动物会经历巨大的适应性变化，包括心率和呼吸频率降低以及核心体温从 37°C (98.6°F) 降低到 4°C (39°F)。 ，但它们不会经历寒冷引起的疼痛，尽管一年中有八个月处于寒冷、无功能和缺氧状态，但它们的器官仍能继续发挥功能。此外，在冬眠期间，动物不喝水；因此，冬眠者必须完全依靠内部资源的管理和利用才能长期生存，该项目旨在利用一系列尚未开发的尖端工具和方法，了解冬眠者在没有水的情况下生存数月的分子机制。这项研究的结果将具有广泛的科学意义，包括更好地了解所有哺乳动物共有的调节内部水和离子平衡的一般机制。背景下的努力一个课外教育项目（感觉生理学俱乐部），旨在向来自康涅狄格州、纽约州和马萨诸塞州的初中和高中生宣传人类和动物生理学的科学知识。互动实验活动超出了大多数学校的科学课程。这项研究的主要科学目标是通过研究地松鼠在细胞、分子和回路水平上拓宽我们对哺乳动物体液稳态的有限理解。该项目测试了地松鼠通过改变下丘脑轴来忍受长期缺水的假设，下丘脑轴控制口渴并介导抗利尿激素的释放。该提案的具体目标包括研究支持释放的神经机制。该项目结合了细胞、分子和生物学层面的研究，并使用了一系列工具和方法。学科：神经肽和激素的国家特异性生化分析、激素产生的定量分析、差异转录组学、激素释放的电子显微镜和形态测量分析以及饮酒行为的行为分析该项目的一个主要创新方面是光遗传学的使用。 、纤维光度测定和电生理学工具以前没有用于冬眠动物，这项研究的结果将描述液体离子平衡微调的一般原理，提出了一种策略。在没有水的情况下维持生命，并预测是否可以诱导其他哺乳动物冬眠。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Ground squirrels initiate sexual maturation during hibernation

地松鼠在冬眠期间启动性成熟

• DOI: 10.1016/j.cub.2022.02.032
• 发表时间: 2022-04
• 期刊: Current Biology
• 影响因子: 9.2
• 作者: Dai Pra, Rafael;Mohr, Sarah M.;Merriman, Dana K.;Bagriantsev, Sviatoslav N.;Gracheva, Elena O.
• 通讯作者: Gracheva, Elena O.

Towards understanding the neural origins of hibernation

理解冬眠的神经起源

• DOI: 10.1242/jeb.229542
• 发表时间: 2022-01
• 期刊: Journal of Experimental Biology
• 影响因子: 2.8
• 作者: Junkins, Madeleine S.;Bagriantsev, Sviatoslav N.;Gracheva, Elena O.
• 通讯作者: Gracheva, Elena O.

Cellular, Molecular, and Physiological Adaptations of Hibernation: The Solution to Environmental Challenges

冬眠的细胞、分子和生理适应：环境挑战的解决方案

• DOI: 10.1146/annurev-cellbio-012820-095945
• 发表时间: 2020-10
• 期刊: Annual Review of Cell and Developmental Biology
• 影响因子: 11.3
• 作者: Mohr, Sarah M.;Bagriantsev, Sviatoslav N.;Gracheva, Elena O.
• 通讯作者: Gracheva, Elena O.

Ground squirrels

地松鼠

• DOI: 10.1016/j.cub.2022.02.015
• 发表时间: 2022-06
• 期刊: Current Biology
• 影响因子: 9.2
• 作者: Pra, Rafael Dai;Bagriantsev, Sviatoslav N.;Gracheva, Elena O.
• 通讯作者: Gracheva, Elena O.