Adaptation and acclimatization to altitude in newborn rodents.

生活在高海拔(2500米)的哺乳动物(包括人类)面临着严重的后果，因为氧气的可用性(O2)减少。最古老的动物和人类种群在这种环境中至少进化了数千年，现在被认为是从基因上适应了海拔。最近，在过去的500到50年里，低地迁徙在北美、南美和西藏建立了新的定居点，并(无论是有意还是无意)将新的哺乳动物物种引入海拔。令人着迷的是，观察到对这些人和动物群体中的大多数人和动物来说，适应海拔是一个持续的过程。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，我们正在比较低氧水平对大鼠和小鼠的影响。这两个物种之所以有趣，是因为它们都是在过去的几个世纪里被引入南美洲的，它们都表现出了不同的成功：只有老鼠在高海拔和低海拔地区定居，而老鼠仍然是唯一的低海拔物种。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学研究所(Ibba，La Paz，海拔3600米)的同事以及我们在魁北克的实验室进行的研究表明，成功地适应海拔高度密切依赖于出生后发育期间的氧气供应。我们发现，当新生大鼠暴露在低氧环境中时，它们的肺部会受到永久性的损害，这会降低氧气从肺部流向血液的速度。在类似的条件下，新生小鼠的肺损伤要小得多。此外，当哺乳动物暴露在低氧气水平下时，他们能够“过度换气”(增加他们呼吸的气量)。这种反应是由大脑的特殊部分(呼吸控制系统)调节的，有助于将更多的氧气带到肺部。我们的实验表明，暴露在低氧环境中的新生小鼠能够过度换气，但这种反应在新生大鼠中不那么重要。有趣的是，人类婴儿和新生儿对低O2水平的不同反应也被用来解释为什么不同的人类群体在高原有不同的适应。为了解释这些差异，我们需要了解低O2水平是如何引发生物反应的。在细胞水平上，哺乳动物拥有能够感知氧气水平的分子，并在氧气水平下降时引发特定的反应。这些系统存在于肺部和呼吸控制系统中，但到目前为止，它们在推动适应海拔变化方面的确切作用还不完全清楚。我们的主要假设是，在大鼠和小鼠身上，这些机制对低氧气的反应是不同的。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。这些研究涉及广泛的生命科学，包括生理学和遗传学，但也包括生态学和进化论，因为他们的目标是确定解释两种啮齿动物海拔分布的机制。它们还为学生提供了一个丰富而刺激的挑战，他们将必须执行要求苛刻的技术方法，并了解他们的数据如何适合这一迷人的研究领域。

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.