Naked Mole Rats May Unlock Secrets About The Human Brain

IRA FLATOW: This is Science Friday. I’m Ira Flatow.

If there was ever a controversial nominee for the cute animal award, it would be the naked mole rat. It’s not everyone’s cup of tea. It’s bald, mostly hairless with pink, wrinkly skin, long front teeth that they can use for digging. They’re kind of funny-looking.

But they have wonderful biological talents. Consider. They live in underground colonies that you could easily confuse for an ant’s nest– one queen and all her children. They are remarkably resistant to cancer. That’s cool, potentially useful to know. And they can go without oxygen for 18 minutes. You’ve got to love them.

And adding to all that cuteness, new research has another mole rat mystery to explain. They seem to need high levels of carbon dioxide or else they have seizures. Explain that! And we will.

Here to explain why this quirk of naked mole rats may help humans, and especially children, is Dr. Dan McCluskey, a neuroscientist and associate professor of psychology at the City University of New York in, well, New York. Welcome, Dan.

DAN MCCLUSKEY: Thanks, Ira. Great to be with you.

IRA FLATOW: This is such a strange thing to say about mammals, that they need carbon dioxide, when it’s usually such a poison, right? We exhale it.

DAN MCCLUSKEY: Yeah. We consider it waste, and most other animals do, you know? Except for a few strains of bacteria, nobody is really relying on carbon dioxide. But yeah, as you said, our research seems to suggest that they’re relying on it for keeping their brain balanced.

IRA FLATOW: How did you figure this out in the first place?

DAN MCCLUSKEY: Yeah. So it took a while for us to pull it all together. So one of the things that we’ve been doing is tracking whole colonies of naked mole rats in captivity where we have 40, 50, 60 animals. And we’re looking at all the micro movements that each animal makes through the colony. And for a while we thought that they were completely bored, that they wouldn’t move, sort of no matter what we did, we’d give them some food, or some warmth, or some shelter elsewhere, and they would just no matter what, they would always go right back to the same location, and just pile on each other.

But then when we did another experiment where we put CO2, carbon dioxide, in another area of their environment, it was the only thing that we could use to draw them out. And so we were really surprised that they were actually attracted to it.

IRA FLATOW: And so there’s the mystery. Why would an oxygen-breathing mammal be attracted to lower oxygen environments and like the CO2?

DAN MCCLUSKEY: So we think that this provides what we would consider a proximate cause for eusociality. We think that this is driving them–

IRA FLATOW: Say that again.

DAN MCCLUSKEY: A proximate cause for eusociality. So like you mentioned, they’re eusocial. So they’re really unusual for mammals in that they have a queen and a breeding male. And rather than do what most mammals do, which is grow up, and leave the nest, and start their own colony, these guys stick around. So the older brothers and sisters stay around for multiple generations, and help raise the young.

And it’s been sort of a mystery of how this comes about. But the data that we have seems to suggest that maybe they’re relying on the carbon dioxide to help balance their brain. And this way if they ever venture above ground, they start feeling a little bit anxious or worse, they could have an epileptic seizure. And that might get them to return to the nest rather than go off on their own.

IRA FLATOW: That’s interesting. So it has something to do with living underground, and their brain has adapted to that.

DAN MCCLUSKEY: Yeah. So one of the things that we see over and over again with these guys is that they require very– a lot of their adaptations seem to reduce the need for energy. So they live in this real underground very stuffy environment. So a lot of the things that they’ve adapted over the 35 million years of their existence has been to kind of reduce their oxygen needs, reduce their caloric intake, and all of these things.

And so what we think happened is over millions of years as they evolved, they developed ways where they can rely on less oxygen. Eventually, they sort of used it as a crutch where they would use the high carbon dioxide to keep the brain balanced.

So it’s been known for since at least the 1,500s that carbon dioxide itself does a good job of suppressing brain activity. And so the naked mole rats figured out a long time ago that if they have the carbon dioxide, they don’t need some of the things that you and I have in our brains to suppress activity.

IRA FLATOW: Now, isn’t it some sort of a– usually a vulnerability in rodents that are immature, but as they get older, they leave this sort of need, but not happening in the mole rats.

DAN MCCLUSKEY: That’s exactly right. So a lot of the things that we see in these strange adaptations for mole rats is that they seem to maintain baby brains throughout their whole life. And their life is long. They live 30 years, which is a really long time for a small rodent. This tolerance for CO2, which they have, is something that small humans and other small mammals have early in childhood, but most of us grow out of it. These guys seem to have a mutation that keeps them in this sort of infantile brain state that allows them to keep this high CO2 tolerance.

IRA FLATOW: Now, you mentioned that like bees they live in colonies, and there’s a queen there. Has the queen grown up out of the baby state?

DAN MCCLUSKEY: It’s a really great question. Apart from all the mysteries of naked mole rats, one of the real mysteries is, how do they ever start new colonies? You’ve got this multiple generations, hundreds of animals that live together below ground, and very little evidence that they ever go above ground. One of the big mysteries that remains is how do new colonies get started.

And so there is this sort of mystical character called the dispersive morph, which gains a lot of fat, gets a pale appearance, and we think is storing up energy so that it can go above ground. And with the data we’ve seen, it looks like the dispersive morph grows up very quickly, that the brain grows out of this phase. And they’re able to tolerate normal air, just like you or I. And we think it’s a temporary switch, that once they go below ground and start their own colony, that they go back to this baby brain state again. And so we’re really interested in the mechanisms that’s driving that.

IRA FLATOW: Quite interesting. I was talking– before we were talking about the seizures. And of course, is there a takeaway from this for diagnosing or understanding human seizures?

DAN MCCLUSKEY: There is. So before the age of five, children are prone to what are called febrile seizures, which are seizures that occur under conditions of high fever. And our collaborators at the University of Helsinki showed in 2006 that those seizures arise from breathing fast. So as you and I and everyone else gets into a warm environment, or when we feel a fever coming on, we start breathing faster to lose some of that hypothermia. For most of us, the brain can balance that perfectly well.

But for babies and for young children, and particularly young children that have a mutation in this gene called KCC2, we see that they can’t tolerate the changes and the loss of carbon dioxide. And so this is exactly what’s happening in the naked mole rats. They have a mutation in this KCC2 gene that’s keeping them in this immature state. And as a result, whenever they lose carbon dioxide, they run into trouble. And they have these fever-induced seizures. And so we think by studying the naked mole rats we might be able to better understand what’s going on in the children, where these seizures are emanating from the brain, and ultimately what we might be able to do to treat them.

IRA FLATOW: Quite interesting. I’m going to get in trouble for saying that mole rats are such weird animals, because they are a fan favorite on the Sci Fri staff. Everybody loves them here.

How is it that they’re also so relevant to medical research? I mentioned their resistance to cancer earlier. Mammals, is this related to that energy-saving adaptation you mentioned earlier?

DAN MCCLUSKEY: Yeah. I think so. And I think there’s a lot of commonalities between humans and naked mole rats. When you first look at them, you might not think so, but the more you study them, they’re the humans of the rodent world, in many ways. They’re hairless compared to their closest relatives. They’re a lot more social. They live a lot longer, just like humans do.

We have seemed to adapt some of the same features over the years. And so we do share a lot of genes in common with naked mole rats. And by studying their genome and differences in that, we might be able to understand a little bit more about ourselves.

IRA FLATOW: And how are your mole rats doing right now? Are you able to take good care of them?

DAN MCCLUSKEY: Great question. We have a really great staff, our frontline workers who are going in and caring for the mole rats every day. And I’m happy to report that they’re doing really well.

We have a live video feed of one of our nests. And I check in on them at least once a day to see how they’re doing. And I think they’re quite happy to be left alone for a little while.

IRA FLATOW: When I had my little ant colony as a kid, I had to actually put them underground. The ant colony has a little bit of soil in it that they dig and burrow under. Do you have to supply that for the mole rats, too?

DAN MCCLUSKEY: We give them some basically corn cob and some other materials. They really like paper. They like to use paper to build their nests.

One of the things that’s fun to do is we put all these little radio frequency identification chips under the skin of every single animal. So we have about somewhere around 250, 300 animals. And each one has this unique EZ-Pass-type chip under their skin. And we’re tracking all their movements.

But it’s fun to put the chips inside of paper and cardboard, and other things like that, and see who’s doing the nest building, and sort of figure out what each of their roles is in the colony. And so by using this technology, we can actually answer questions about their behavior and their tasks in the colony.

IRA FLATOW: Are they curious? Do they like to explore things if you leave stuff out?

DAN MCCLUSKEY: They do.

IRA FLATOW: Yeah?

DAN MCCLUSKEY: They do. Yeah, they love to explore. No matter what we give them, they’ll spend a few hours really investigating it.

And they have a pretty interesting communication system where they can sort of bring back information to the nest and communicate to the other mole rats. And so it’s fun to put some new object in part of their environment and watch them kind of send messages to each other about going to check it out, and see them all start to gravitate towards it. It’s pretty fun to watch.

IRA FLATOW: Now, I hear that your tape recorder that you use in recording your audio has naked mole rat teeth marks on it. Is that correct? That is correct.

DAN MCCLUSKEY: We’re really interested in the communication tools that they use. Unlike mice and rats that use sounds that we can’t hear– they’re in a higher frequency range than what we can hear– naked mole rats have chirps that are audible.

And there is a sort of telltale indicator that something’s going on where all of the members in the nest will start to emit this sort of high frequency chirp. And when that happens, very interestingly, the queen seems to kind of come towards the nest wherever she is in the colony. And she really does spend a minute investigating all the animals in the nest. And then finds one in particular and shoves it out. And we think that this is related to this dispersion, that she’s selecting animals to be pushed out of the colony.

And so, yeah, we’ve put recording devices in just to try to get at this type of recording, and break it down, and figure out if there’s ways that we can detect it. And just like everything else, they’re going to chew on it. And so you have to be careful with what you put in. And you can’t be too linked to things, because they will get eaten, for sure.

IRA FLATOW: So you’re saying that the queen actually expels some of her children from the nest?

DAN MCCLUSKEY: There’s a really interesting movie, I think, to be made, Ira, on the naked mole rats, and not a documentary, but some story to be told, because, yeah, the queen seems to– there’s this– while they’re good at communication, there are certain things that I think they can’t communicate.

So what we think is that the queen is specifically selecting members of the colony to go on and disperse and start their own colony. And the way that we think this happens is that she’s banishing them from the colony nest in some ways to habituate them to normal air so that they can go above ground and start their own colony.

And so there’s this– if you watch these animals that are banished from the nest, they’ll linger for a while, and then eventually try to go back to the nest. And then this whole experience will happen where the animals chirp, and the queen will shove them out. And then the animal just looks completely defeated.

And there’s this kind of really beautiful story where the mother is selecting them to be the next queen. And they can’t express that. And they’re sort of banished from the nest. Meanwhile, they’re the champion of the group that’s going on to spread the genes. So it’s a really fascinating kind of story there.

IRA FLATOW: I see a great animated feature here, you know? You know what I’m talking about?

DAN MCCLUSKEY: I do. I wish I had the skill to do it.

IRA FLATOW: About the naked mole rat that gets banished from the nest and goes on to do great things.

DAN MCCLUSKEY: That’s right.

IRA FLATOW: Is there is there something that you’d like to know in your research about naked mole rats that you don’t know but would like to find out.

DAN MCCLUSKEY: We are really interested in this. We’re all in a position where I think we’re getting more pale and putting on more fat these days. Whatever the mechanism is that drives that really fascinates me, this idea of why an animal is selected to become a disperser.

And why I think it’s so fascinating is because if we can figure it out, if we can figure out what changes in the body of these animals, they’re switching for a two-week period from naked mole rats to humans essentially. They’re adapting our traits, and our features, and tolerating our air.

Ultimately, as we talked about, the people who may have a similar disposition and maybe some problems with tolerating carbon dioxide, or low levels of carbon dioxide, whatever the mole rats are doing they’ve solved the problem. So if we can study them and see how they’re solving the problem, it might teach us something about how we can help ourselves.

IRA FLATOW: Just a reminder that I’m Ira Flatow, and this is Science Friday from WNYC Studios, talking about the weird, wonderful world of naked mole rats with neuroscientist Dan McCluskey.

And something I’ve been fascinating with as we’ve been speaking here, they live in colonies from like bees or ants. If you study bees or ants, can you learn something about how the colonies of naked mole rats might be behaving?

DAN MCCLUSKEY: They do seem to have certain features that are really interesting and common. For example, we look at something in the brain called neuropeptide Y, which we see is different in some of our animals that help to stick around and build the nest versus animals that are likely to go out and forage and try to find new food.

And that neuropeptide Y difference is also seen in honeybees, that the drone bees have higher levels of neuropeptide Y, the ones that are out and foraging, just like we see. So that was really fascinating, because they don’t have any commonality in the genome, but we’re seeing some of the same mechanisms that are driving different behaviors in a eusocial group.

IRA FLATOW: Are you a neuroscientist who got interested in mole rats or were you first a mole rat fan who got interested in neuroscience?

DAN MCCLUSKEY: I am the former. In 2006, for Christmas I got a Fact-A-Day calendar from my sister-in-law. And I made it– every day I would get to a new page on the calendar. And April 17 of 2007 I saw this comment about a naked mole rat, and that it was neither a mole nor a rat, and is the only cold-blooded mammal.

And as a neuroscientist at the time who was interested in studying febrile seizures and how heating the brain might cause seizure activity, I thought it would be a really interesting model where we can take room temperature, take a cold-blooded mammal that has a brain similar to ours, and see what happens. And man, 13 years later, I couldn’t believe how well it mimics what happened in the humans in the same state.

And so I had never heard of a naked mole rat back then until I got to that calendar post. And then it just changed my life forever.

IRA FLATOW: My only other question I would have for you is, what do you say to people who really think they’re ugly?

DAN MCCLUSKEY: They’re certainly polarizing. Nobody doesn’t have a reaction to them. Either people think they’re really cute or really ugly.

And we’ve had a lot of the ugly camp come into the lab and start to work with them. And they’ll change their mind pretty quickly.

I guess one of the things I’m fortunate about is that I get to spend a lot of time with them. So when I first brought them back and started them in my lab in 2010, I would bring in a desk, and a laptop, and a chair, and just sit there, and work on my grading, and work on my papers, and do everything in the room, and just sit and observe them.

And it really is remarkable. You have a whole community that you’re just watching and seeing how they interact with one another. And I don’t do that much anymore, because we keep it pretty warm in there, because they are nearly cold-blooded. And so you’ll break a sweat sitting in there if you’re in there long enough. But it’s hard to think that they’re ugly if you spend enough time with them, I think.

IRA FLATOW: Well, these has been a truly fascinating discussion. I’ve learned a whole bunch of stuff. Even in the last stuff you talked about cold-blooded, warm-blooded mammals, I never knew that. Thank you very much, Dan McCluskey for taking time to be with us today.

DAN MCCLUSKEY: It’s been great, Ira. Thank you very much.

IRA FLATOW: Dan McCluskey is a neuroscientist and an associate professor of psychology at the City University of New York.

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