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: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=630915
• 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.

哺乳动物（包括人），生活在高海拔（> 2,500 m）的情况下，由于氧气的可用性降低而面临严重的后果（O2）。在这种环境中，最古老的动物和人类人口至少已经发展了数千年，现在被认为是普遍适应高度的。最近，在过去的500至50年中，低地移民在北美和南美和西藏建立了新环境，并将新哺乳动物物种（有意）引入了高度。令人着迷的是，对于大多数这些人类和动物人群适应高度是一个持续的过程。与更古老的人群相比，这些人群中的一些人对海拔高度的适应不佳。我们的研究旨在了解成功适应高度的成功与失败之间的差异。为此，我们正在比较大鼠和小鼠中低O2水平的影响。这些物种很有趣，因为它们在过去几个世纪中都在南美引入，并且已经显示出不同的成功：只有小鼠才殖民了高海拔和低海拔地区，而大鼠仅仍然是低地物种。是什么造成这种差异？我们最近的工作与玻利维亚海拔生物学研究所的同事（IBBA，LA PAZ，海拔3600m，海拔3600m），在魁北克实验室中，表明，成功适应高度的我们在产后发育过程中的成功适应高度取决于O2的可用性。我们发现，当新生大鼠暴露于低O2时，它们的肺部遭受了永久性损害，从而降低了O2从肺部流向血液的速率。在类似条件下，新生小鼠的肺部受损得多。另外，当暴露于低O2水平时，哺乳动物能够“过度换气”（增加呼吸的空气量）。该反应是由大脑的专业部位（呼吸控制系统）介导的，并有助于将更多的氧气带入肺部。我们的实验表明，暴露于低O2的新生小鼠能够过度换气，但是这种反应在新生大鼠中的重要性要小得多。有趣的是，还引起了人们对人类和新生儿中低O2水平的不同反应，以解释为什么不同的人口在高度上具有不同的适应性。要解释这些差异，我们需要了解低O2水平如何诱导生物学反应。在细胞水平上，哺乳动物具有可以感知O2水平的分子，并在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，它们在推动适应高度的精确作用尚未完全理解。我们的主要假设是，这些机制对大鼠和小鼠的低O2响应方式有所不同。我们将使用几种分子生物学工具来更准确地了解这些差异及其后果。这些研究与包括生理和遗传学在内的一系列生命科学以及生态学和进化有关，因为它们旨在识别解释2种啮齿动物物种中高度分布的机制。他们还为学生提供了丰富而刺激的挑战，他们将必须采取苛刻的技术方法，并了解他们的数据如何适合这一引人入胜的研究领域。