Acclimatization and adaptation to high altitude in newborn rats

生活在高海拔(即2500米以上)的哺乳动物面临着两个主要限制，因为氧气水平和环境温度都很低。因此，成功地适应海拔需要足够的反应，以改善氧气的运输、扩散和利用，但也需要保持足够的体温调节(生物体在寒冷环境中保持较高内部温度的能力--哺乳动物必须的能量消耗)。高海拔对新生哺乳动物有很大的影响，因为相关的低氧暴露极大地推迟了生长，并通过与动物的遗传背景相互作用，有助于“塑造”成年哺乳动物的表型。然而，虽然我们已经扩展了关于出生后慢性缺氧对呼吸控制发育的影响的知识，但关于体温调节发育和晚年对高原的长期适应的数据很少。我们在长期生活在高海拔地区(玻利维亚拉巴斯海拔3600米)的大鼠身上获得的初步结果表明，慢性低氧极大地推迟了出生后体温调节的建立，这可能对生殖成功不利。由于一些啮齿动物(Permyscus manulatus，或鹿鼠)在高海拔地区很常见(与大鼠相反)，并且被认为是遗传上对低氧适应的，我们假设这些物种的新生儿在高原上表现出快速的体温调节发育，不会受到出生后低氧的长期影响。因此，该项目的长期研究目标是更好地了解环境氧暴露与适应高原的遗传背景之间的复杂关系。我们的研究将有助于更好地了解高原动物和人类聚落的自然历史。这是高海拔生理学的一个经典方面，正如公认的描述所表明的那样，在早期殖民时期，第一个欧洲血统的孩子花了50多年才在波托西市(海拔4000米以上--在一个原住民居住在高海拔地区的地区)存活下来，在那里试图建立一个永久的定居点。

Mammals living at high altitude (i.e. above 2500m) are facing two main constrains as oxygen levels and ambient temperature are low. Accordingly, successful adaptation to altitude requires adequate responses to improve oxygen transport, diffusion and utilization, but also preserve adequate thermoregulation (the ability of an organism to maintain a high internal temperature in a cold environment - an obligatory energy expenditure in mammals). High altitude has a potent impact in newborn mammals, since the associated hypoxic exposure drastically delays growth, and by interacting with the genetic background of the animal, contributes to "shape" the adult phenotype. However, while we have extended knowledge on the impact of chronic postnatal hypoxia on respiratory control development, data on thermoregulation development and on the long-term acclimatization to altitude later in life are scarce. Our preliminary results obtained in rats permanently living at high altitude (3600m above sea level, La Paz, Bolivia) suggest that chronic hypoxia drastically delays the postnatal establishment of thermoregulation, which could be detrimental for reproductive success. Because some rodents (peromyscus maniculatus, or deer-mice) are common at high altitude (as opposed to rats), and are considered as being genetically adapted to hypoxia, we hypothesize that the newborn of these species would exhibit fast thermoregulatory development at altitude, and would not be affected by the long-term effect of postnatal hypoxia. Accordingly, the long-term research objectives of this project are to better understand the intricate relationship between environmental oxygen exposure and genetic background for acclimatation at high altitude. Our studies will help to better understand natural history of animals and human settlements at altitude. This is a classical aspect of high altitude physiology, as shown by the well established account that during the early colonial period it took more than 50 years before the first child of European origin survived in the city of Potosi (above 4000 m - in a region populated by native high altitude populations), as Spanish where trying to establish a permanent settlement