Cancer-resistant, pain-tolerant and long-lived naked mole-rats (Heterocephalus glaber) are one of nature's most remarkably resilient creatures, earning them superhero status among animal researchers. Of course, all superheroes need a secret lair and for naked mole-rats, this lair is an underground burrow bustling with up to 300 other mole-rats. These crowded conditions often contain elevated levels of CO2 (up to 2.3% versus 0.04% in the atmosphere), which would be difficult for many mammal species to endure. It was previously thought that naked mole-rats had forcibly adapted a tolerance to these high CO2, or hypercapnic, conditions, but a recent study by a team of neuroscientists from the New York campus of The City University of New York, USA, has revealed that naked mole-rats don't just tolerate these harsh hypercapnic conditions – they are key to their survival.
In mammals, brain activity is partly regulated by gamma-aminobutyric acid (GABA) neurotransmitters, which stop the brain from becoming overstimulated and causing debilitating seizures. However, after analysing the naked mole-rat genome, the team of researchers was fascinated to find that this supposed super-species had a significant weakness in their ability to use GABA neurotransmitters to prevent seizures, thanks to a single mutation. Given mole-rats lack this important cog in the neurological machine, do their uniquely hypercapnic living arrangements help in shielding them from convulsions?
The researchers placed naked mole-rats in semi-natural laboratory colonies and watched their behaviour in response to different CO2 concentrations. They also implanted the mole-rats with small radio transmitters, allowing them to track where the mole-rats spent their time within the colony. They quickly realised that the mole-rats preferred to spend time in chambers with the highest levels of CO2, and when the CO2 was reduced in one burrow chamber and increased in another, the mole-rats relocated their main huddling burrows to the new hypercapnic hot-spot.
This curious result spurred the team on to investigate the naked mole-rats’ susceptibility to seizures outside of their burrow, so they constructed a test chamber that could recreate the environmental conditions of both underground and surface environments of the rodents’ East African habitat. They also implanted some of these mole-rats with electroencephalogram electrodes, allowing them to measure the animals’ brain activity and look for signs of seizures. When exposed to fresh outside air and a temperature of 42°C, mimicking above-ground conditions, 90% of the mole-rats showed signs of seizures, but none of these signs appeared when the fresh air was replaced with the higher-CO2 burrow air. Instead of causing drowsiness and confusion, as would normally be expected in mammals, the high CO2 conditions of the burrows actually helped to prevent neurological overstimulation and maintain a balanced brain.
It appears that on the surface (literally), the naked mole-rats’ impaired neurotransmitters are a serious handicap to survival, but underground, they serve as an important energy-saving mechanism that allows the rodents to rely less on the costly chemical processes that regulate their brains and more on the freely available CO2 in their burrows. The researchers propose that this niche adaptation is probably why naked mole-rats tend to avoid leaving and starting new burrows. Intriguingly, the same genetic mutation has also been identified in humans and is associated with febrile seizures, epilepsy and schizophrenia, leading the authors to consider the applications of this research for human healthcare. With these new insights into the role of this mutation in seizure-related conditions, perhaps hypercapnia holds potential for anticonvulsant treatment, because – as naked mole-rats can attest – a breath of fresh air can sometimes do more harm than good.