The Brain’s Glial Cells Might Be As Important As Neurons

IRA FLATOW: This is Science Friday. I’m Ira Flatow. I’ve got a tiny bit of trivia for you. You ready? What kinds of cells are in the brain?

Now, you probably thought of neurons, right? And you’d be right– well, half the time. Half of the cells in the brain are neurons. But the other half are what are called glial cells. You ever heard of them? And when scientists first discovered them over a century ago, they thought that the glial cells simply held the neurons together. And their name derives from a Greek word that means “glue.”

But in the past decade, researchers have come to understand that glial cells do so much more. They communicate with neurons. They work closely with the immune system. And they even play an important role in regulating our gut, yes.

Joining me now to give us a crash course in glial cells is my guest, Yasemin Saplakoglu, staff writer at Quanta Magazine. She’s based in New York City. Welcome to Science Friday.

YASEMIN SAPLAKOGLU: Hi. Thanks for having me.

IRA FLATOW: So nice to have you. For all of us, can you give us a glial cell 101, please?

YASEMIN SAPLAKOGLU: Yes, I’d love to. So when we think about the brain, we typically think neurons. And that makes total sense. Neurons are truly the stars of the nervous system. They fire signals, basically, helping us navigate our internal and external worlds, like my thoughts, my dreams, my ramblings. They’re all created by neurons. They’re glamorous cells.

But like you said, about half of the central nervous system, which is the brain and the spinal cord, is actually made up of other types of cells called glia. And glia is basically a catch-all term for all the cells that aren’t neurons. And there are many different types, sizes, shapes. Some look like stars. Some are bushy. Some are sheath-like. There are Schwann cells that wrap around nerve fibers and insulate them, astrocytes that direct flow of fluid in the brain, microglia that act like immune cells in the brain. There’s just so many different forms and functions of glia.

IRA FLATOW: And how are they different than– from neurons?

YASEMIN SAPLAKOGLU: So the biggest difference between neurons and glial cells is that neurons are the ones that send electrical signals in the brain. They’re the ones that drive our cognitive processes, like I said, whereas glia– they’re– one source once told me they’re electrophysiologically “boring.”

[CHUCKLING]

But I wouldn’t call them boring.

So they were thought for a long time just– to just be support cells for neurons, nourishing and cushioning them, but not really doing too much else. And that’s, of course, changed now. And the role of glia has undergone a renaissance of some sort in the last decades.

IRA FLATOW: It reminds me of the old phrase “junk DNA.” Wait a minute, DNA really does something. And now we’re learning the same thing about the glial cells.

YASEMIN SAPLAKOGLU: Totally.

IRA FLATOW: So tell us, what’s the latest that glial cells can do? Once the scientists thought that, as you say– that only the brain cells are capable of sending electrical signals. But there’s new research that shows that the glia might also be capable of doing this?

YASEMIN SAPLAKOGLU: Yeah. So that research– it’s actually really neat. So it was in 1990 that researchers observed in a dish that an astrocyte, which is, like I said, a type of glial cell, the most common type, responded to a neurotransmitter called glutamate, which is a neurotransmitter that typically generates electrical activity. It triggers it in neurons. So when a neuron signals to another neuron, it releases neurotransmitters. And that triggers the next neuron to fire.

And in the decades since, researchers– some groups said glial cells can signal like this, too. And some groups said they couldn’t. And then last fall, there was a new paper that came out that showed the best evidence yet that they could actually do this. They showed images of glutamate flowing from astrocytes and genetic data suggesting that they had the cellular machinery to do this. And that opens up the possibility that some astrocytes might form an essential part of the brain circuitry. And it would mean that they can receive information from neurons and potentially feed it back to other neurons.

But there’s still so much we don’t know about when glia are signaling. If they’re signaling, how are neurons responding? Why do only some glia seem to signal? That was the other thing that they found– was that it was only a subset that could signal, which reconciled those two different sides of the argument.

IRA FLATOW: And what is the purpose of their signaling?

YASEMIN SAPLAKOGLU: These are all questions that we’re still unpacking.

IRA FLATOW: Might this research upend how scientists think the brain works?

YASEMIN SAPLAKOGLU: Yeah, totally. There’s a lot that they’re finding, really different functions that glia are playing that’s upending this neuro-centric view of the brain. There’s clearly a lot that glia are doing. And I would say that most neuroscientists would now agree that we need to be looking at glia in order to understand these really fundamental processes of the brain.

IRA FLATOW: I know there’s another subtype of glia called microglia proving to be really important. Tell us about those.

YASEMIN SAPLAKOGLU: So microglia has also received a lot of interest in the last decade or so. They’re thought of like immune cells of the brain. They respond to brain trauma and other injuries and suppress inflammation. They mimic macrophages of the immune system by engulfing threats in the brain, like cellular debris or microbes.

They also do a bunch of things, like maintain neuron networks. They’ll break connections between neurons that are obsolete. They regulate brain development, which is also a huge thing.

IRA FLATOW: And there was a case of a child born without these type of cells and the brain was all sorts of disorganized. Has that case helped us understand about the importance of the microglia?

YASEMIN SAPLAKOGLU: Yeah. So The Atlantic wrote about that, actually, a few years ago. The young boy didn’t have any microglia, which was a crazy case study. And they found that when they looked into his brain, his neurons ended up in all the wrong places and made the wrong connections. And this really showed how important these cells are for the brain’s development.

And other studies previously in lab dishes or in animals showed that microglia can shepherd developing neurons to the right locations in the brain. And they can prune connections between neurons that need cutting. So they’re really deeply involved in the development of these neuronal networks.

IRA FLATOW: I want to move to talk about glia in another part of the body because we always talk about the microbiome and the gut. The gut is chock-full of nerves, too, right? How do we think about the role they play in second brain?

YASEMIN SAPLAKOGLU: Yes. So this is really cool. So the revelation that glia are doing all of these different things in the brain is now happening in a parallel movement in the gut. It’s a newer movement, but the same thing. A moment of recognition has come.

So we have a brain in our gut. It’s called the enteric nervous system, or sometimes the second brain. From the moment you swallow your food to the moment it leaves your body, the gut works to move it through the different factories of digestion. It’s an incredibly critical process and one that requires a ton of coordination across dozens of cell types and tissues. And that coordination comes from the enteric nervous system, which, just like in the brain, is made up of neurons and glia. And they weave through the intestinal walls. And they coordinate all of these different functions so that digestion happens properly.

And again, for over a century, we’ve known that enteric glia exist. But we didn’t really know what they did. And of course– surprise, surprise– now we know that they do a lot. And studies have now pointed to so many different roles that they play in digestion and nutrient absorption and blood flow and immune responses.

We know that they’re among the first responders to injury and inflammation. They help maintain the gut’s barrier to keep toxins out. They just do a bunch of different things.

IRA FLATOW: How could we not know this stuff over all these years? You know what I’m asking? We say we’re so smart about neurology and whatever and not know something really basic like the gut.

YASEMIN SAPLAKOGLU: I think it’s mostly because of the advances in cell bio-techniques that we’ve started to really understand and be able to untangle the forms and the functions of glia, like new imaging techniques and fluorescent labeling and genetic manipulation. We didn’t have all of those decades ago or, to the extent of how advanced they are today, we didn’t have those advanced methods back then. So it was hard to disentangle– first of all, it was hard to figure out what glia were doing independently from neurons because they’re so entangled.

IRA FLATOW: Let’s talk some more about this research that shows that the glia actually sense when food moves through the digestive tract. Do we know how they do that?

YASEMIN SAPLAKOGLU: Yeah. So that was a really cool piece of new research. So there was this group that was looking into trying to figure out the diversity of glia that exists in the gut because that’s another really cool aspect, which is what are the subtypes of glia, what are they each doing. And while they were really digging into this, they found a subtype that they dubbed hub cells.

And they found that those hub cells are actually able to sense force. And this is something that neurons can do to sense food in the intestines and move it along. But they didn’t know before that glia can also do this, which is really fascinating. At least a subset of glia are involved with helping to move food along.

IRA FLATOW: Because they sense the force. Maybe that’s what they sense when you get punched in the stomach.

YASEMIN SAPLAKOGLU: Maybe.

IRA FLATOW: Maybe. If they sense– they can sense force inside, maybe they can sense that kind of impact. I imagine that if we better understand the role of glial cells, especially when we’re talking about the gut there– that we might have– we might come up with better treatments for what– gastrointestinal disease, autoimmune disorders?

YASEMIN SAPLAKOGLU: Yeah, absolutely. And that’s a huge area of effort that’s going on right now– is to target glia, whether in the gut or in the brain, because as we’re learning all of these new functions that glia are applying, scientists are realizing that they could potentially be a good target for these various problems that happen. And in the gut particularly, because glia are known to control the activity of immune cells, they’re suspected to play a role in a lot of gastrointestinal disorders and diseases, which make them a good target. And like I said earlier, they have been found to be among the first responders to injury or inflammation in the gut while this experiment was in the mouse gut. And tampering with them could lead to an inflammation response.

IRA FLATOW: Yeah, because we know how important inflammation is, whether it’s autoimmune disorders or what. And that might be really good finding.

YASEMIN SAPLAKOGLU: Right. Exactly.

IRA FLATOW: What do we still not understand about glia? What do we need to know? It’s probably too big a question. But I have to ask it.

YASEMIN SAPLAKOGLU: Oh, yeah. There’s so much that we still don’t understand about glia. So one thing is just the nuances of how they’re interacting with neurons. Neurons and glia can’t function independently. Their interactions are critical for the survival of the nervous system and everything generated within it. But their partnership is still mysterious. What is directing what? What’s the cause and effect?

And then there’s also the other question of the diversity of glial cells. How many subtypes exist? And what exactly do those subtypes do in the brain and the gut? And some of the researchers that I talked to were focusing on that question specifically because they thought maybe those subtypes could be dysfunctioning in a different way for different diseases.

And then, of course, there’s the translational aspects. Can we actually target glia to treat some of those neurodegenerative conditions or gut disorders? And how well will those treatments be? I think it’s really exciting, not to say that neurons aren’t exciting. They’re extremely exciting. But now we can say glia are cool, too.

IRA FLATOW: If you study neurons and you’re a neurologist, what do you call yourself if you study glia?

YASEMIN SAPLAKOGLU: A “gleeful” scientist?

IRA FLATOW: [CHUCKLING]

I think that’s it. I think you’ve coined a new word, a new phrase. I guess the interesting part here is that scientists realize that this is something new they have to study if they want to understand the whole nervous system.

YASEMIN SAPLAKOGLU: Yeah. And I think it’s going to take some time to start looking at glia for everything you’re studying. It’s not quite there yet. But I think that a lot of people do appreciate the importance of including glia in studies or really trying to unpack what they’re doing for various processes.

IRA FLATOW: If glial cells do so many different things, are we making a mistake lumping them all together as one type of cell?

YASEMIN SAPLAKOGLU: So I think this is an interesting question. And I think there is a group of scientists that are arguing that, no, they shouldn’t be lumped into the same type of cell because they do so many different things.

Yes, there’s some commonality. But it’s– I feel like lumping it into one term is sort of like looking at a bowl of fruit and saying, these are all banana-like things, or these are all fruit. It gets the point across. But an orange is totally different than a banana. So that’s an interesting question to ask. And I think that a lot of people think that, yes, we shouldn’t be naming it all as a singular term.

IRA FLATOW: If you could predict the future of how we understand glial cells, can I get a– hazard a guess of what’s coming next?

YASEMIN SAPLAKOGLU: What’s coming next? I think that we are going to really start to be able to look at– well, I hope, I should say, that we’ll really start to be able to look at the interactions between neurons and glia to really get at what this communication is. And especially in the gut, I think it’ll be really important to understand how the glia are chatting with all of these different systems and what that conversation is leading to.

How is the glia talking to microbes and the microbiome? There’s so much to unravel. What is the molecular mechanisms behind that? What are they saying? What are they talking about? What are they doing?

IRA FLATOW: So interesting. And you wrote all about this in Quanta Magazine. I want to thank you for taking time to be with us today. Fascinating stuff. And good luck to you.

YASEMIN SAPLAKOGLU: Thank you so much for having me. It was a pleasure.

IRA FLATOW: Yasemin Saplakoglu, staff writer at Quanta based in New York City.

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