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

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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.