FRIMEDBIO-Fri prosj.st. med.,helse,biol

While medical science has had a very limited success in counteracting the deleterious effects of ischemia/hypoxia in humans, evolution has repeatedly solved this problem. The best studied examples of anoxia tolerant animals are some North American freshwa ter turtles (genera Trachemys and Chrysemys) and a Scandinavian freshwater fish, the crucian carp (no: Karuss, lat: Carassius carassius). This proposal is a continuation of a long standing research effort in my group, together with international collabora tors, to clarify the mechanisms underlying the ability of these vertebrates to survive weeks to months without any oxygen. We now focus on two problems that urgently need attention. (1) Do anoxic crucian carp get tissue damage and repair it? This is a ver y basic question that has long been put aside due to the general assumption that anoxia tolerant vertebrates survive anoxia by protecting their tissues from anoxia induced damage. We and others have now evidence that make us hypothesize that anoxia tolera nt animals do indeed suffer from increased cell death, and that the brain is effectively repaired following an anoxic episode. This would of course make them very interesting models for studying how evolution has solved the problem of regenerating damaged neural tissue. (2) The function of the hypoxia inducible factor (HIF) in hypoxic and anoxic crucian carp is not understood. HIF function is intensively studied, as HIF is generally regarded as the master switch for initiating hypoxia responses in animals . While HIF is usually seen as a savior molecule in hypoxic situations, our preliminary results turn this on its head by indicating that the crucian carp has to suppress HIF function during hypoxia and that this could be the norm for animals capable of su rviving prolonged hypoxia because many HIF mediated functions become energetically too expensive and maladaptive. We will examine hypoxia-induced changes in HIF levels and how HIF is regulated in crucian carp.