When the brain goes diving: Biochemical mechanisms conveying hypoxia tolerance to brain neurons of diving animals

潜水哺乳动物和鸟类的大脑在淹没时反复暴露在低氧环境中。冠状海狮（Cystophora cristata）的脑神经元比小鼠更耐缺氧。我们发现，这种耐受性可能是由于氧化能量代谢的转变密封星形胶质细胞，而在陆地哺乳动物有氧能量生产发生在神经元。鲸鱼没有表现出这种变化，但在它们的大脑中有更高水平的呼吸蛋白质脑红蛋白。在体外，缺氧的海豹脑神经元在葡萄糖中比在乳酸中存活更长。大鼠和海豹的大脑在对抗活性氧（ROS）的防御策略上表现出明显的差异，包括更高水平的超氧化物歧化酶2。为了了解大脑缺氧耐受的代谢策略，我们将采用免疫组织学和生物化学方法来研究海豹和鲸鱼有氧和无氧能量途径的成分分布。为了确定耐缺氧的出现，我们还将研究浅潜水的斑海豹。采用脑切片的体外研究将揭示神经元糖原储存和星形胶质细胞摄取乳酸的贡献，以及对氧气的需求。我们将通过研究防御酶的水平和分布来进一步研究海豹和鲸鱼的ROS保护。我们的研究将揭示哺乳动物大脑缺氧耐受的共同和不同的策略。

The brains of diving mammals and birds are repeatedly exposed to low oxygen periods when submerged. Brain neurons of the hooded seal (Cystophora cristata) are more hypoxia tolerant than those of mice. We showed that this tolerance may be due to a shift of oxidative energy metabolism to seal astrocytes, while in terrestrial mammals aerobic energy production takes place in neurons. Whales do not display this shift, but have much higher levels of the respiratory protein neuroglobin in their brains. In vitro, hypoxic seal brain neurons survive longer in glucose than in lactate. Rat and seal brains showed clear differences in defence strategies against to reactive oxygen species (ROS), including a higher level of superoxide dismutase 2. To understand the metabolic strategies of the brain's hypoxia tolerance, we will employ immunohistological and biochemical methods to investigate the distribution of components of aerobic and anaerobic energy pathways in seals and whales. To identify the emergence of hypoxia tolerance, we will also study the shallow diving harbour seal. In vitro studies employing brain slices will unravel the contribution of neuronal glycogen stores and lactate uptake by astrocytes, and the requirements for oxygen. We will further investigate ROS protection in seals and whales by studying the levels and the distribution of defence enzymes. Our studies will reveal common and divergent strategies of hypoxia tolerance of the mammalian brain.