In the animal kingdom, certain animals avoid the cold winter weather by either migrating to warmer regions, growing thick fur or hibernating, while others tolerate bitter temperatures by literally freezing solid. In addition to allowing 60–70% of their body to freeze, animals like the wood frog (Lithobates sylvaticus) have an amazing superpower, which we have yet to understand: they can survive for months without oxygen, because when they freeze, they stop breathing. How they do it and how they recover from such a challenge are just two of the questions that today's researchers are asking.

Undeterred by working in cold weather, or perhaps just not appreciating the 4–6 week period of warm weather that Ottawa, Canada, enjoys each year, Rasha Al-Attar and Ken Storey from Carleton University, Canada decided to explore the mechanism behind the wood frog's ability to tolerate no oxygen (anoxia) for a day at 5°C and then recover. To this end, the team captured male wood frogs from ponds around Ottawa and acclimated them to 5°C for two weeks prior to testing. To induce the anoxic condition, the team bubbled nitrogen gas in an experimental chamber for 15–20 min to displace the oxygen; they then added the frogs, placed the boxes at 5°C and started their timer. At the 24 h mark, they immediately collected liver and muscle samples from a group of frogs, while allowing another group to recover in air for 4 h, before collecting the same tissues.

Based on previous research on wood frogs performed by Storey's team, which had shown that the animals are able to decrease their metabolism when they have no access to oxygen, Al-Attar and Storey decided to determine what causes this reduction in metabolism by exploring the expression levels of a protein called nuclear factor of activated T-cell (NFAT), which plays a key role in regulating cell metabolism and cell death. The authors found that the four isoforms of the protein (known as NFATc1–NFATc4) are expressed differently in the liver compared with the muscle in response to anoxia and recovery. In addition, the team determined that NFATc4 may play an essential role in helping the liver recover from oxygen deprivation, but that the muscle may use other metabolic pathways to prevent tissue damage from the lack of oxygen. It appears that NFAT proteins may not be as essential in muscle as they are in the liver.

Al-Attar and Storey's study is unique, because it highlights some of the mechanisms that wood frogs use not only to survive anoxia and freezing, but to do so while incurring minimal tissue damage. Now imagine if we could harness this frog superpower and use it to reduce tissue damage in humans following a stroke – when the brain is deprived of oxygen – which may cause paralysis, or use it to preserve organs during transport from a donor to a recipient. The possibilities are endless! Who would have thought that we would have so much to learn from such a small creature as the wood frog?

K. B.
Effects of anoxic exposure on the nuclear factor of activated T cell (NFAT) transcription factors in the stress-tolerant wood frog
Cell Biochem. Function