Discovered less than a decade ago, and reported in all vertebrate phyla,the function of the oxygen-binding neuronal heme protein neuroglobin has yet to be determined. Suggested roles include oxygen storage or transport,regenerating NAD+ under anaerobic conditions, or acting as a scavenger of toxic reactive oxygen species. Very low oxygen levels (hypoxia)increase neuroglobin levels in the mammalian brain, and neuroglobin increases reduce the damage following experimentally induced stroke in animal models. However, its oxygen binding characteristics and low tissue concentrations suggest that neuroglobin is not primarily an oxygen storage compound. The apparent pro-survival role of neuroglobin under low oxygen conditions led Terrie Williams and her colleagues at the University of California Santa Cruz to wonder whether diving mammals, which naturally experience levels of hypoxia that would cause brain damage in most vertebrates, express higher levels of neuroglobin than non-divers.

The team compared the brain protein neuroglobin and the more widespread cellular cytoglobin in both diving and terrestrial animals: eight kinds of stranded or humanely killed dolphins and whales, two pinnipeds and the sea otter, plus coyotes, foxes, bobcats and mountain lions from government trapping programs (or roadkill). They measured total globin protein content from gray matter samples and then calculated the neuroglobin/cytoglobin levels by subtracting the hemoglobin absorbancy from the total globin content. The researchers also determined neuroglobin and cytoglobin mRNA levels for the mountain lion, bobcat, and five marine mammal species.

Diving marine mammals are known to have higher blood oxygen carrying capacities, and this was reflected in the group's results. Brain hemoglobin levels were higher in marine mammals compared with terrestrial ones, with a near 10-fold difference in hemoglobin concentration between mountain lions and the pelagic diving pilot whale. Similarly, there was a 3-fold range in neuroglobin/cytoglobin levels among the 16 species tested, with a distinct clustering of terrestrial, swimming and diving specialists. Surprisingly,though, neuroglobin levels were not highest in the divers but in the swimmers,which generally dive for short periods only but spend time in fast, aerobic swimming. There was in fact an inverse relationship between neuroglobin levels and maximum dive time in marine mammals. Williams' group thus hypothesized that deep divers rely preferentially on circulating globins while `sprinters'enhance intracellular globin stores.

Interestingly, a link between activity level and intracellular heme proteins is supported by the terrestrial exception to the rule: the bobcat had neuroglobin levels comparable to swimming specialists and significantly higher than other terrestrial animals. The bobcat is an ambush predator rather than a good swimmer, so a high globin level in both groups implies that the neuroglobin is not associated with hypoxia tolerance but instead benefits highly active species.

The authors suggest that neuroglobin facilitates oxygen movement from blood to neural tissues and thus provides a secondary level of neuronal protection from hypoxia in animals that cannot significantly increase circulating hemoglobin levels. Diving mammals can increase the number of circulating red blood cells because the decreased heart rate and vasoconstriction typical of divers ameliorate the negative impact of highly viscous blood, and thus divers can maintain oxygen gradients even in hypoxia. Active sprinters, with elevated heart rates and blood flow, instead appear to increase intracellular globin levels to ensure adequate oxygen delivery, because you can't catch the prey if you pass out on the way!

Williams, T. M., Zavanelli, M., Miller, M. A., Goldbeck, R. A.,Morledge, M. C. D., Pabst, D. A., McLellan, W., Cantin, L. P. and Kliger, D. S. (
). Running, swimming, and diving modifies neuroprotecting globins in the mammalian brain.
Proc. R. Soc. B