Science Friday - The Brain’s Glial Cells Might Be As Important As Neurons

Episode Date: April 15, 2024

Half of the cells in the brain are neurons, the other half are glial cells.When scientists first discovered glia over a century ago, they thought that they simply held the neurons together. Their name derives from a Greek word that means glue.In the past decade, researchers have come to understand that glial cells do so much more: They communicate with neurons and work closely with the immune system and might be critical in how we experience pain. They even play an important role in regulating the digestive tract.Ira is joined by Yasemin Saplakoglu, a staff writer at Quanta Magazine who has reported on these lesser-known cells.Transcripts for each segment will be available after the show airs on sciencefriday.com. Subscribe to this podcast. Plus, to stay updated on all things science, sign up for Science Friday's newsletters.

Have you ever heard of glial cells? They make up about half of the cells in your brain. The role of glia has kind of undergone a renaissance of some sort in the last decades. It's Monday, April 15th, and we're keeping our brain cells firing because this is Science Friday. I'm sci-fi producer Shoshana Buxbaum. When scientists first discovered glia over a century ago, they thought that they simply held the neurons together. Their name derives from a Greek word that means glue. But in the past decade or so, researchers have come to understand that glial cells do so much more.

They communicate with neurons and work closely with the immune system. And they even play an important role in regulating our guts. Here's Iroflato with more. Joining me now to give us a crash course in glial cells is my guest, Yasmin Soplo Kulo, staff writer at Quantum Magazine. She's based in New York City. Welcome to Science Friday. Hi, thanks for having me.

So nice to have you. Okay, for all of us, can you give us a sort of glial cell one-on-one, please? Yes, I'd love to. So when we think about the brain, we typically think neurons, and that makes total sense, right? 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, you know, 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, like some look like star, some are fushy, some are sheath-like. There are, you know, swan cells that wrap around nerve fibers and insulate them, astrocytes that direct flow of fluid in the brain, microglia, that kind of act like immune cells in the brain. there's just so many different forms and functions of glia.

And how are they different then from neurons? Yeah. 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 kind of, you know, one source once told me, they're kind of electrophysiologically kind of quote-unquote boring. But I wouldn't call them boring.

So they were thought for a long time to just sort of be, you know, 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 Glea has kind of undergone a renaissance of some sort in the last decades. Now, it kind of reminds me of the old phrase junk DNA. Wait a minute, you know. DNA really does something. And now we're learning the same thing about the glial cells.

Totally. Yeah. Okay. So tell us what's the latest that glial cells can do? I mean, 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? Yeah, so that research, it's actually really neat.

So it was in 1990 that researchers observed kind of 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, you know, in a decade since researchers, you know, some groups said, you know, 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 kind of 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, you know, 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 so like, you know, so much we don't know about when glia are signaling. If they're signaling, how are neuroids, neurons responding, you know, why do only some glia seem to signal? That was the other thing that they found was that there was only a subset that could signal, which reconciled those two different sides of the argument. Right. And what is the purpose of their signaling? Yeah. I mean,

these are all questions that were still unpacking. Might this research abend how scientists think the brain works? Yeah, totally. I mean, there's a lot that they're finding really, you know, different functions that glia are playing that's kind of upending this like neurocentric view of the brain. Like 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 like really fundamental processes of the brain. I know there's another subtype of glia called microglia. Yeah. Proving to be really important to tell us about those. Yeah. So microglia has also received a lot of interest in the last decade or so. They're thought of kind of like immune cells of the brain.

They respond to brain trauma and other injuries, a suppress inflammation. They sort of mimic macrophages of the immune system by like engulfing threats in the brain, like cellular debris or microbes. They also, you know, 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. And there was a case of a child born without these type of cells, and the brain was all sorts of disorganized? I mean, has that case helped us understand about the importance of the microglia? 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 sort of ended up in all the wrong places and made the wrong connections. And this really kind of 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 kind of 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, you know, the development of these neuronal networks. I want to move to talk about Glea 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? I mean, how do we think about the role they play in second brain? Yes, so this is really cool. So the revelation that glia are doing all of these

different things in the brain is now sort of happening in a parallel movement in the gut. It's like a newer movement, but the same thing, right? 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. You know, from the moment you swallow your food to the moment it leaves your body, the gut works to move it through like the different factories of digestion. It's an incredibly critical process and one that requires a ton of coordination like 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, you know, neurons and glia. and they weave through the intestinal walls and they coordinate all of these different functions

so that digestion happens properly. And, you know, again, for over a century, we've known that entercglia exists, 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, like, digestion and nutrient absorption and blood flow and immune responses. You know, 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. 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, not know something really basic like the gut? I think it's mostly because of the advances in cell biotechiques 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. Like we didn't have all of those decades ago or to the extent of like 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 kind of hard to like figure out what glia were doing independently from neurons because they're so entangled. Let's talk some more about this research that shows that the glee actually sense when food moves through the digestive tract. Do we know how they do that?

Yeah. So that was a really cool piece of kind 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, you know, to sense food and the intestines and kind of move it along. But they didn't know before that glia can also do this, which is really fascinating.

So they, like at least a subset of glia are involved with helping to move food along. Because they sense the force. Maybe. Maybe that's what they sense when you get punched in the stomach. Maybe. Maybe. 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, right? That we might have, we might come up with better treatments for what, gastrointestinal disease, autoimmune disorders? 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 like we are applying, scientists are realizing that they could potentially be a good target for these various, you know, problems that happen.

And in the gut, particularly, because Gle are known to kind of control the activity of immune cells, they're suspected to play a role in a lot of like astrointestinal disorders and diseases, which make them, you know, a good target. And like I said earlier, they have been found to be, you know, among the first responders to injury or inflammation in the gut while this experiment was in the mouse gut. and tampering with them could, you know, lead to an inflammation response. Yeah, because we know how important inflammation is, whether it's autoimmune disorders or what. And that might be a really good finding.

Right. Exactly. What do we still not understand about Glea? What do we need to know? It's probably too big a question, but I have to ask it. Oh, yeah. I mean, 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. Like 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 like still kind of mysterious. Like what is directing what? Like 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, you know, some of the researchers that I talked to were, like, focusing on that question specifically because they thought maybe those subtypes could be dysfunctioning in, like, a different way for different diseases. And then, of course, like, there's the translational aspects. Like, can we actually target glia to treat some of those neurodegenerative conditions or gut disorders and how well will those treatments be? I mean,

I think it's, like, really exciting. I mean, I mean, mean, not to say that neurons aren't exciting. They're extremely exciting. But like now we can say glia are cool, too. If you study neurons and you're a neurologist, what do you call yourself if you study glia? A gleeful scientist? That's it. I think you've coined a new word. Yeah. 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. Yeah. And, you know, I think it's going to take some time to, you know,

start looking at glia for like everything you're studying. It's not quite there yet. But I think that a lot of people do appreciate the importance of, you know, including glia and studies or really kind of trying to unpack what they're doing for various processes. If glial cells do so many different things, are we making a mistake lumping them all together? as one type of cell?

Yeah. 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. Like, yes, there's like some commonality, but it's sort of, 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. I mean, it gets the point across, but like orange is totally different than a banana. But so yeah, 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 like a singular term. If you could predict the future of how we understand glial cells, can I get a

hazard a guess of what's coming next? Yeah, 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, we'll really 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, you know, conversation is leading to. You know, how is the glia talking to microbes and the microbiome? You know, there's so much to unravel. Like, what is the molecular mechanisms behind that? what are they saying? What are they talking about? What are they doing?

So interesting. And you wrote all about this in Quanta magazine. I want to thank you for taking time to view with us today. Fascinating stuff. And good luck to you. Thank you so much for having me. It was a pleasure. Jasmine Saplakulo, staff writer at Quanta based in New York City. That's all the time we have for today. Lots of folks helped make the show happen, including Sandy Roberts, George Harper. Annie Nero Jason Rosenberg

Tomorrow we'll take a field trip to visit a scientist out in Colorado who's studying a mite that's threatening the survival of honeybees I'm sci-fry producer Shoshana Bucksbaum catch you next time