Adaptation and acclimatization to altitude in newborn rodents.

新生啮齿动物对海拔高度的适应和适应。

• 批准号: RGPGP-2014-00083
• 负责人: Joseph, Vincent
• 金额: $ 2.26万
• 依托单位: Université Laval
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Group
• 财政年份: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=610520
• 关键词: Adaptation; acclimatization; altitude; newborn; rodents.

Mammals (human included), living at high altitude (>2,500 m) face serious consequences due to the reduced availability of oxygen (O2). The oldest animal and human populations have evolved at least for thousands of years in this environment, and now are considered as being genetically adapted to altitude. More recently, over the past 500 to 50 years, lowland migrants have established new settlements in North and South America and in Tibet, and have introduced (intentionally or not) new mammalian species to altitude. It is fascinating to observe that for most of these human and animal populations adaptation to altitude is an ongoing process. Some of these populations show poor adaptation to altitude compared to the more ancient populations. Our research is designed to understand the differences between a successful and a failed adaptation to altitude. To this aim, we are comparing the effects of low O2 level in rats and mice. These species are interesting because they have both been introduced in South America in the past centuries, and they have shown divergent success: only mice have colonized the high and low altitude regions, while rats remain exclusively a lowland species. What causes this difference? Our recent work performed with our colleagues of the Bolivian Institute for Altitude Biology (IBBA, La Paz, 3600m above sea level), and in our laboratory in Québec, showed that successful adaptation to altitude is tightly dependent on O2 availability during postnatal development. We have found that when newborn rats are exposed to low O2 their lungs suffer permanent damages, which reduces the rate at which O2 flows from the lungs to the blood. Under similar conditions the lungs of newborn mice are much less damaged. In addition, when exposed to low O2 levels, mammals are able to "hyperventilate" (increase the volume of air they are breathing). This response is mediated by specialized parts of the brain (the respiratory control system) and helps bring more oxygen to the lungs. Our experiments have shown that newborn mice exposed to low O2 are able to hyperventilate, but this response is much less important in newborn rats. Interestingly, divergent responses to low O2 levels in human infants and newborn have also been evoked to explain why different humans population have different adaptation at altitude. To explain these differences, we need to understand how low O2 level can induce biological responses. At the cellular level, mammals possess molecules that can sense O2 level, and induce specific responses when it decreases. These systems are present in the lung and in the respiratory control system, but so far their precise role in driving adaptation to altitude is not completely understood. Our leading hypothesis is that these mechanisms are responding differently to low O2 in rats and mice. We will use several molecular biology tools to understand more precisely these differences and their consequences. These studies are relevant for a broad array of life sciences including physiology and genetics, but also ecology and evolution, because they aim at identifying the mechanisms explaining altitude distribution in 2 rodent species. They also provide a rich and stimulating challenge for students, who will have to perform demanding technical approaches and understand how their data fits into this fascinating field of research.

生活在高海拔 (>2,500 m) 的哺乳动物（包括人类）由于氧气 (O2) 的可用性减少而面临严重后果。最古老的动物和人类种群在这种环境中已经进化了至少数千年，现在被认为在基因上已经适应了海拔高度。最近，在过去的 500 到 50 年里，低地移民在北美、南美和西藏建立了新的定居点，并将新的哺乳动物物种（有意或无意）引入了高海拔地区。令人着迷的是，对于大多数人类和动物群体来说，适应海拔高度是一个持续的过程。与更古老的种群相比，其中一些种群对海拔的适应能力较差。我们的研究旨在了解成功和失败的海拔适应之间的差异。为此，我们正在比较低氧气水平对大鼠和小鼠的影响。这些物种很有趣，因为它们在过去的几个世纪中都被引入南美洲，并且表现出不同的成功：只有老鼠在高海拔和低海拔地区定居，而老鼠仍然是低地物种。 造成这种差异的原因是什么？我们最近与玻利维亚海拔生物研究所（IBBA，拉巴斯，海拔 3600 m）以及我们魁北克实验室的同事进行的研究表明，成功适应海拔高度取决于出生后发育过程中氧气的供应情况。我们发现，当新生大鼠暴露在低氧气环境中时，它们的肺部会遭受永久性损伤，从而降低氧气从肺部流向血液的速度。在类似的条件下，新生小鼠的肺部受到的损害要小得多。此外，当暴露于低氧气水平时，哺乳动物能够“过度换气”（增加呼吸的空气量）。这种反应是由大脑的特殊部分（呼吸控制系统）介导的，有助于为肺部带来更多的氧气。我们的实验表明，暴露在低氧气环境中的新生小鼠能够过度换气，但这种反应对于新生大鼠来说并不那么重要。有趣的是，人类婴儿和新生儿对低氧气水平的不同反应也被用来解释为什么不同的人群在海拔高度有不同的适应。 为了解释这些差异，我们需要了解低氧气水平会如何引起生物反应。在细胞水平上，哺乳动物拥有可以感知氧气水平的分子，并在氧气水平降低时诱导特定反应。这些系统存在于肺部和呼吸控制系统中，但到目前为止，它们在驱动适应海拔高度方面的确切作用尚不完全清楚。我们的主要假设是，这些机制对大鼠和小鼠的低氧气含量的反应不同。我们将使用几种分子生物学工具来更准确地理解这些差异及其后果。 这些研究与广泛的生命科学相关，包括生理学和遗传学，也与生态学和进化论相关，因为它们的目的是确定解释两种啮齿动物物种海拔分布的机制。它们还为学生提供了丰富而刺激的挑战，学生必须执行要求严格的技术方法，并了解他们的数据如何适应这个迷人的研究领域。