Molecular adaptations of the brain of diving mammals to hypoxia

点击翻译按钮获取中文摘要

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.