Adaptation and acclimatization to altitude in newborn rodents.

生活在高海拔地区的哺乳动物（包括人类）由于氧气（O2）的减少而面临严重的后果。最古老的动物和人类种群已经在这种环境中进化了至少数千年，现在被认为是遗传上适应了海拔。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（有意或无意地）向高原引入了新的哺乳动物物种。令人着迷的是，对于大多数人类和动物种群来说，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。这两个物种很有趣，因为它们都是在过去的几个世纪里被引入南美洲的，它们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，而老鼠仍然是一个专门的低地物种。是什么导致了这种差异？我们最近与玻利维亚高原生物学研究所（IBBA, La Paz，海拔3600米）的同事以及我们在quacimenbec的实验室进行的工作表明，成功适应海拔高度与出生后发育期间的氧气供应密切相关。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损伤，这会降低氧气从肺部流向血液的速度。在类似的条件下，新生小鼠的肺部受到的损伤要小得多。此外，当暴露于低氧水平时，哺乳动物能够“过度通气”（增加呼吸的空气量）。这种反应是由大脑的特定部分（呼吸控制系统）调节的，它有助于给肺部带来更多的氧气。我们的实验表明，暴露在低氧环境下的新生小鼠能够过度通气，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氧水平的不同反应也被唤起，以解释为什么不同的人类群体对海拔有不同的适应。*为了解释这些差异，我们需要了解低氧水平是如何引起生物反应的。在细胞水平上，哺乳动物拥有能够感知氧气水平的分子，当氧气水平降低时，它们会引起特定的反应。这些系统存在于肺和呼吸控制系统中，但到目前为止，它们在驱动海拔适应方面的确切作用尚未完全了解。我们的主要假设是，这些机制对大鼠和小鼠的低氧反应不同。我们将使用一些分子生物学工具来更精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，但也与生态学和进化有关，因为它们旨在确定解释两种啮齿动物海拔分布的机制。他们还为学生提供了丰富而刺激的挑战，他们将不得不执行苛刻的技术方法，并了解他们的数据如何适合这个迷人的研究领域。

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.