Acclimatization and adaptation to high altitude in newborn rats

在高海拔地区，大多数哺乳动物的机体会做出一系列调整，增加血液中氧气的运输和细胞对氧气的利用。这些反应包括通气量的逐渐增加，其在几天内发展，这是由于感测血氧减少的专门细胞的灵敏度的逐渐增加。此外，这些反应随年龄而变化（新生儿低，成人强），这种发展受到环境氧气水平的极大影响。在低氧条件下（如发生在高海拔地区）饲养的人类和动物在这些细胞对低氧的反应能力方面存在持续和矛盾的缺陷，因此它们的呼吸反应比预期的要弱。我们的目标之一是进一步了解这种对低氧的呼吸敏感性的降低如何阻止成年人对长期低氧的充分适应。这个问题对于全世界生活在海拔2500至4500米的数亿人来说是很有意义的。我们研究的第二个问题涉及低氧对长期生活在高海拔地区的大鼠出生后发育的影响，该地区位于海拔3600米的玻利维亚首都。虽然在成年人中对长期暴露于低氧的反应有很好的描述，但在新生儿中的研究很少，但对于更好地了解哺乳动物和人类如何在高海拔生存和发育成适应良好的成年人至关重要。我们使用在高海拔地区饲养的大鼠来确定高海拔缺氧在出生后发育过程中的作用，这是成功繁殖的关键时期。遗传适应有利于高海拔地区的生活，在北美极高的海拔（4500米）发现了一些遗传适应的啮齿动物。为了了解遗传背景和在高海拔地区出生后发育过程中的贡献，我们将研究这些动物呼吸控制的发展。这些研究将扩展我们对高海拔成功生活的机制的理解，这是生理学和呼吸生物学长期感兴趣的研究领域。

At high altitude, the organism of most mammals responds with a series of adjustment that increases the transport of oxygen in the blood and its utilization by the cells. These responses include a gradual increase of ventilation, that develops over several days, due to a progressive increase of sensitivity of specialized cells sensing the decrease of blood oxygenation. Furthermore these responses varies with age (low in newborn and strong in adults), and this development is greatly influenced by environmental oxygen levels. Humans and animals raised under condition of low oxygen (such as occurring at high altitude) have a persistent and paradoxical defect in the ability of these cells to respond to low oxygen, hence their respiratory response is weaker than expected. It is one of our objective to further understand how this decrease of respiratory sensibility to low oxygen will prevent an adequate acclimatization to long-term hypoxia in adults. This question is of interest for the hundreds of millions of humans living at altitude ranging from 2500 to 4500 m worldwide. A secondary question of our research concerns the effect of low oxygen during postnatal development in rats permanently living at high altitude, in the capital-city of Bolivia, at 3600m above sea level. While responses to long-term exposure to low oxygen are well described in adults, studies in newborn are scarce, but are nonetheless critical to better understand how mammals, and men, may survive and develop into well-adapted adults at high altitude. We use rats raised at high altitude to define the contribution of high altitude hypoxia during postnatal development, a critical period for succesful reproduction. Genetic adaptation favors life at altitude, and some genetically adapted rodents are found at extremely high altitude in North America (4500 m). To understand the contribution of genetic background and during postnatal development at high altitude we will study development of respiratory control in these animals. These studies will expend our comprehension of the mechanisms underlying successful life at high altitude, a research area of long-lasting interest in physiology and respiratory biology.