Neuronal hypoxia tolerance in diving endotherms

Abstract

The thesis “Neuronal hypoxia tolerance in diving endotherms” sheds light on mechanisms giving diving animals, such as the hooded seal, impressive dive capabilities of 1 hr duration down to 1000 m depth. In spite of enhanced capacity to store oxygen in their body and an ability to reduce their oxygen-consumption, these animals can resurface with blood oxygen values so low that a human being in the same situation would loose consciousness within seconds. This implies that the brain of diving animals tolerate lack of oxygen much better than the brain of non-diving animals. In the thesis it is demonstrated for the first time that this is actually the case. <br/>Electrophysiological recordings of isolated brain slices were used to investigate how neuronal activity changed in response to hypoxia in brain tissue from hooded seals (Cystophora cristata) (Folkow et al., 2008) and eider ducks (Somateria mollissima) (Ludvigsen & Folkow, 2009). Results showed a significant higher survival of brain tissue from the diving species relative to non-diving controls. <br/>Follow-up experiments were performed in order to investigate whether ATP-sensitive potassium channels (KATP-channels), that previously have been demonstrated to offer short-term protection against oxygen- and energy deprivation in other species, play a role in the neuronal hypoxia tolerance of the diving animals. The KATP-channels were pharmacologically blocked in hypoxic tissue, and comparison of responses to that of un-manipulated tissue indicated that the ion-channels offer some protection, but that they are not solely responsible for the high hypoxia tolerance in brain tissue from the divers. <br/>Investigating capillary density in the hooded seal brain, it was found that the hooded seal has a higher, or similar, capillary density compared to much smaller mammals. This is not expected from capillary density scaling laws, and may indicate that the hooded seal benefits from a higher capillary density than more similar sized mammals that may contribute to the hypoxia-tolerance of hooded seals. <br/>The electrophysiological investigations also gave new information on how coordinated network activity may arise in the mammalian brain. Earlier investigations have indicated that such rhythms are dependent upon neural connections between different brain regions and therefore can be studied only in the intact brain. Working with thick, isolated brain slices from hooded seals it was discovered that rhythmical activity may also arise within smaller neocortical areas, which may contribute to understanding how intrinsic brain activity is regulated.