Molecular adaptations of the brain of diving mammals to hypoxia

充足的氧气供应对生命是必不可少的。像海豹和鲸鱼这样的潜水哺乳动物可以忍受反复和长时间的缺氧。它们的大脑能在低氧环境下存活，而低氧环境对包括人类在内的大多数哺乳动物来说都是致命的。在体外实验中，帽海豹的神经元可以在缺氧的情况下忍受几个小时，同时也可以忍受低葡萄糖和高乳酸水平。此外，斑海豹的大脑在星形胶质细胞中显示出不寻常的氧化代谢定位。潜水哺乳动物为研究哺乳动物大脑对缺氧和再氧化的分子适应提供了独特的机会。我们将采用比较转录组学方法，选择海豹和鲸鱼以及它们的陆地亲戚。我们将通过检测阳性选择、基因扩增和脑特异性基因的差异表达来确定候选基因。比较RNAseq还将提供有关基因相互作用和网络调整的信息。代谢组学将用于研究潜水和非潜水哺乳动物大脑中的能量代谢。对细胞培养物中与潜水相关的基因进行分析将提供有关其特定功能的信息。我们将解开海豹与非潜水哺乳动物相比，神经元和神经胶质细胞任务分布的差异，这可能有助于大脑的生存。总之，这些结果将为大脑如何在缺氧和缺氧/再氧化中生存提供见解，并将提高对哺乳动物大脑能量代谢的理解。

A sufficient supply of oxygen is essential for life. Diving mammals such as seals and whales tolerate repeated and prolonged hypoxia. Their brains survive low oxygen levels that would be fatal to most other mammals, including humans. In vitro, neurons of the hooded seal endure several hours without oxygen, as well as low glucose and high lactate levels. Further, the hooded seal brain displays an unusual localisation of the oxidative metabolism in astrocytes. Diving mammals offer the unique opportunity to study the molecular adaptations of the mammalian brain to hypoxia and reoxygenation. We will apply a comparative transcriptomics approach employing selected seals and whales along with their terrestrial relatives. We will identify candidate genes by testing for positive selection, gene amplification, and differential expression of brain-specific genes. Comparative RNAseq will also provide information about adjustments in gene interactions and networks. Metabolomics will be used to study the energy metabolism in the brain of diving and non-diving mammals. Analyses of dive-related genes in a cell culture will provide information about their specific function. We will untangle the differences in the task distribution of neurons and glial cells, which may be instrumental for brain survival, in the seal compared to non-diving mammals. Together, the results will provide insights into how the brain survives hypoxia and hypoxia/reoxygenation, and will improve the understanding of energy metabolism in the mammalian brain.