In this episode of Tiny Show and Tell Us, we cover neurogenesis in adulthood (yes! your brain can make new neurons even as you age), the link between exercise and increased neurogenesis in the hippocampus, and the implications that could have for neurodegenerative diseases like Alzheimer's. We continue on our brain-focused episode with the role cerebrospinal fluid plays in cleaning out your brain while you sleep and how its movement is in fact influenced by your brain waves.
Transcript of this Episode
Sam Jones: Welcome to Tiny Show and Tell Us, the bonus series where you write in with your favorite science story, fact, or piece of news, we read your email aloud, and then we dive deeper. I'm Sam Jones. I'm the exec producer of Tiny Matters, and I'm here again with Anne Hylden, who guest co-hosted episode four and who has been doing the research for this bonus series. Hey, Anne, how's it going? Ready for another Tiny Show and Tell Us?
Anne Hylden: I'm so ready. Before we get into today's questions, a reminder that Tiny Matters is always looking for you to write in because that's what makes future episodes possible. You can email tinymatters@acs.org or click the Google form link we put in the episode description. Sam, do you want to go first this time?
Sam Jones: Sure. Today's Tiny Show and Tell Us submission comes from a brother-sister duo, Sunay and Jaansi who are the founders of the LearnOn Podcast, which is the science show by kids for everyone. Thanks so much for your submissions. I'm going to start out with Sunay's. Sunay wrote in saying it's a common myth that the brain stops growing after reaching adulthood. This may not be entirely true. Some research has found the hippocampus, a region responsible for learning and memory, can produce between 700 and 1,500 new neurons each day. The process of neurogenesis is still debated, and there's a lot more to learn about the exact mechanisms by which the brain continues developing, but this could have huge implications on research about Alzheimer's and other degenerative diseases.
So first off, thank you, Sunay. I think this whole topic is really fascinating because. we're going to get into it, but really for a long time, people did think that once you reach a certain age, you're done with creating new brain cells. You were really born with what you were born with, and then if those cells died through aging or some injury, that was that.
Anne Hylden: I know that's what I had been told.
Sam Jones: Oh, yeah, no. I think that was just the understanding for most. It still is the understanding for I think a lot of people, but that's not the case. Let's talk about neurogenesis or the process of making new neurons. Of course neurons, they're cells that make up a lot of our nervous system. During embryonic development, neurogenesis produces billions of neurons. The average brain actually contains around 100 billion brain cells, which is hard to wrap your mind around, and most of them were formed before. Birth neurons come from neural stem cells, which are these self-renewing cells that have the potential to turn into a bunch of different cell types that then make up our central and peripheral nervous systems. So during development, these are the cells that give rise to our entire nervous system.
This process continues throughout, before you're born, after you're born. It does slow down during childhood, slows down way, way more during adulthood, and once a neuron is fully differentiated, meaning it's in its final state, that's permanent, it's not going to divide again. And so when it dies, it dies. It's considered post-mitotic, which means it doesn't undergo the process of mitosis anymore. Mitosis is where you get a duplication of genetic material and then a splitting of the cell to make two cells. So you're not going to get that anymore once you hit the final neuron stage.
So this might've been what contributed to the common misperception that once brain cells die, they can't be replaced. That's it. But neural stem cells persist into adulthood in at least a couple regions of the brain, including the hippocampus. Did you ever hear when you were in school, they would help you remember what the hippocampus did by saying hippos never forget? It was a memory related…
Anne Hylden: I am not familiar with that mnemonic.
Sam Jones: Okay. It's pretty silly, but I always think of it with the hippocampus. The hippocampus, actually, there are two, and they're deep in your brain. They're around an inch-and-a-half above each ear, and they're sort of these curved... You often see them described as like seahorse-shaped structures. The hippocampus is part of your brain that's responsible for your memory and learning and also environmental awareness. So neurogenic activity in the adult hippocampus is really well-established in the literature, at least back into the late '90s. And because the hippocampus is highly impacted in neurodegenerative diseases like Alzheimer's, it's of course a focus. So it's highly impacted, but also it shows the ability to regenerate neurons, or generate new neurons really is what it is.
So in the early stages of Alzheimer's disease, the hippocampus shows really rapid loss of its tissue, and then that's associated with disconnection between the hippocampus and other parts of the brain. So these are really important structures in our brains, and it's also potentially really, really valuable that those structures that are so important and so impacted by something like Alzheimer's might also have the ability to regenerate neurons. So scientists are focusing on studying any effects that neurogenesis may have on memory and if they can improve memory by stimulating it.
So there's a lot that's going on in this field, like a lot. And so it seems like exercise might be a key factor in this neurogenesis in the hippocampus. There are a lot of different research papers showing that exercise lessens cognitive decline in mice by increasing neurogenesis in the hippocampus. So Sunay linked to an article from Harvard Medical School, and in it they interviewed neuroscientist Rudolf Tanzi. And so he and his team at Harvard put healthy young and old mice through different exercise routines on a running wheel. What they were able to gauge is that aerobic exercise induced neurogenesis in these mice, but it also increased this protein called BDNF, or brain derived neurotrophic factor, and it's, I think, pretty well established in the brain as playing an important role in nerve health, helping neurons grow and survive. And actually Dr. Tanzi is quoted in the article saying, "It's like fertilizer to help plant seeds grow."
And so follow-up research has also supported this exercise-neurogenesis link. There was a study that found that adult male rats that did aerobic exercise for eight weeks had two to three times as many hippocampal neurons than rats that didn't exercise.
Anne Hylden: That's a lot.
Sam Jones: Which it seems like a really wild increase. And yeah, it looks like in addition to producing the protein that I just mentioned that helps neurons grow and survive, BDNF, exercise might actually increase production of an enzyme by the liver called GPLD1, and that seems to also have links to neurogenesis. What seems to be very clear is that there is neurogenesis in the brain during adulthood. How that can be modified, or harnessed, or how much exercise, of course, it appears that exercise is playing a role. A lot of stuff with humans is just associative. Right now, a lot of the work is really just done in rats and mice, much harder to test and look for these kinds of things in people because first off, most of it would be inhumane, but then it's just a lot harder to do stuff like this, like really controlled stuff like this.
But yeah, a lot of things are pointing to exercise being an important part of preventing or mitigating dementia and other neurodegenerative diseases like Alzheimer's. The end of the article, there's a discussion about what exercise, because there's also so many variables with that. Do we just all go on long walks or runs, or are we-
Anne Hylden: That's an excellent question.
Sam Jones: Yeah. And so that is unclear at this point. And of course a lot of this information is coming from mice or rats that are running in wheels in a cage in a very controlled environment. So that also complicates things.
Anne Hylden: I imagine them running really fast on their wheels and there's intense workout music playing.
Sam Jones: Yeah, just a really deep base in the background, just keeping them going. Yeah, totally. This researcher, Dr. Tanzi, suggested aiming for 120 to 150 minutes of moderate-intensity exercise per week, things really just that get the heart rate up. But again, I think we all know that some exercise is good for us when we can do it. So nothing groundbreaking in terms of recommendation there, but I do think it's really interesting to be able to see this association and also start to really try and figure out if that is having as much of an impact in people as it is in rats.
Anne Hylden: And also to wrap our heads around the molecular processes behind this. Like you said, we know that exercise is good for us, and potentially we even might know that exercise is good for our brains, but then there's the why, how, what's actually happening, which is a little bit mysterious, and the fact that an enzyme produced in your liver can have a beneficial effect on your brain is a little crazy.
Sam Jones: Yeah, I think in just knowing that so not only are they seeing, "Oh, there's more neurons here," they're seeing there are very specific factors that are now being implicated in that. It also makes you think, "Okay, exercise is good, right? But could there be a way of helping people stave off dementia or Alzheimer's or slow its progression by continuing to get exercise, but then also having some sort of small molecule inhibitor or drug that's going to be beneficial in increasing the levels of BDNF or something like that." So I think it's all very exciting, and it is wild to think that 25, 26 years ago or so, let's say around 25 years ago, we didn't even realize that this was a thing that could happen in the brain. And then just knowing that it happens means that now there's something to work with to try and figure out can we manipulate this process to improve health as we age or post-injury or whatever it may be.
Anne Hylden: Yeah, yeah. Bodies are so resilient.
Sam Jones: Totally.
Anne Hylden: So many mechanisms to heal and repair and all of that. It's amazing.
Sam Jones: Yeah, absolutely. All right, you want to go now?
Anne Hylden: All right, Jaansi has a related topic because it's also about the brain. Jaansi writes, "There's a lot of mechanisms surrounding sleep that we're still really confused about, but one relatively recent discovery that helps us understand a purpose of sleep is centered around cerebrospinal fluid or CSF. This watery liquid flows through the brain and spinal cord, and its functions include providing nutrients, cushioning from injury, and removing waste. That last one is key. The flow of CSF is coupled with brain waves measured during sleep, indicating that it's rhythmic pulsation helps flush out toxins and give your brain an opportunity for recovery. This could be really important for future studies on disrupted sleep, which often indicate neurological and psychological disorders. By looking at CSF patterns during sleep, we might be able to better understand the role of sleep in overall brain health and help prevent such conditions from developing in the first place."
Sam Jones: Cool.
Anne Hylden: Yeah. Thank you, Jaansi, for writing about this, because I find sleep super fascinating. Just the fact that we do it and why and all of that kind of stuff, which, yeah, has also been a little bit mysterious and we're just now getting some clarity on that kind of stuff. I also learned some interesting facts about cerebrospinal fluid. So CSF is very similar to blood plasma. It is continuously produced in the ventricles, which are like little spaces, cavities inside the brain, like deep in the middle. So the CSF comes... I assume it comes out of the bloodstream, into the ventricles, and then from there it flows around the brain tissue, around the spinal cord, until it eventually gets reabsorbed by the blood. And so it's movement, it doesn't have its own pumping system, rather its movement is directed by gravity, and also by our heartbeats. So you can see by MRI, you can see pulses in the cerebrospinal fluid that look like the pulses of a heartbeat, but then also our breathing can cause the CSF to move in different ways and our body movements can also help with that flow.
Sam Jones: Yeah.
Anne Hylden: I learned that a human adult has about 125 milliliters of CSF in their body at any one given time. That's only about a half a cup of liquid. That half a cup is bathing the thin spaces around your brain and around your spinal cord. And as Jaansi wrote, yes, it helps cushion your brain from injury when you have a blow to your head, and it can transport nutrients and waste products. So the CSF gets replaced about every six to eight hours because it's continuously flowing out of the ventricles back into the bloodstream. And so there's this kind of mechanical pulsation in the flow of CSF, but we also have electrical pulsations in our brain, which we call brain waves.
Neurons, the individual brain cells, communicate with each other by sending out ions, and so ions are charged particles. When they move through a fluid, they conduct electricity. And so we have these little tiny electric currents moving from neuron to neuron. But if you put electrodes around someone's scalp, you can see the net result of all these different electrical impulses kind of on a global scale, and that's what we call brain waves. When a person is awake and alert, you can see a lot of very fast oscillations. It's like the needle on a seismograph. It's like going back and forth, kind of crazy. But when someone is asleep or relaxed, those brain waves are much more gradual, more like soft ocean waves up and down and up and down. This has been known for a long time, and you can tell which phase of sleep someone is in by the patterns of their brain waves.
So Jaansi shared a link to a recent article published by scientists who did a study in mice, and they showed that they could use chemicals to flatten out the ionic waves in the brains of sleeping mice. And when they did that, the CSF was less able to actually get into the brain tissue and clear out the waste products. Now, on the other hand, they also did an experiment where they could externally stimulate brain waves, and then when they turned up the amplitude of those brain waves, the CSF was more able to permeate the brain tissue. This is super fascinating to me because I wouldn't have thought that the electrical pulses had anything to do with actually getting the fluid in and out. I would've thought that had to be more about just the mechanical flow. But apparently something about those electrical impulses moving back and forth help the fresh CSF get into the brain tissue and help flush out some of the junk. These researchers propose that there's something about those slow steady waves during sleep that are what help the most.
Sam Jones: Oh, okay.
Anne Hylden: Yeah. So that rather than having a lot of electrical activity, it's the coordination of the brain waves across the brain that is somehow helping. So they point to the fact that these slow brain waves during sleep are a recurring theme across the animal kingdom. And so there must be some adaptational advantage there, and so based on their research, they're proposing it's to help cleanse the brain of waste products.
And I think we already knew that that happens during sleep, that something about the sleep process helps purify whatever has been building up in there.
Sam Jones: Yeah.
Anne Hylden: We just didn't really know how.
Sam Jones: Oh, that's so interesting. There's that phrase, "Sleep on it."
Anne Hylden: Yeah.
Sam Jones: Like you'll make a better decision in the morning. And there is a lot of evidence that our brains, our bodies overall, are repairing and clearing out, and all of these really essential things while we sleep, and that's why sleep is so important. But that just felt so vague, right? It's really cool to see, "Oh no, this is probably actually what's happening that allows for that."
Anne Hylden: Yeah.
Sam Jones: That's so interesting. Very cool. So then I could think of a number of implications potentially for this.
Anne Hylden: I didn't research this specifically for this episode, but I have learned in the past that short sleep or disrupted sleep could contribute to certain neurodegenerative diseases. Like we've known for a long time that Alzheimer's is associated with buildup of certain proteins like in little plaques in the brain. So yeah, that cleaning process might be super important.
Sam Jones: Yeah, absolutely. Well, thank you, Jaansi. As someone who has a biomedical background, but with more of a focus on vaguely like neuroscience, these were kind of my favorite types of...
Anne Hylden: Your jam.
Sam Jones: Yeah, for sure.
Anne Hylden: Thanks for tuning in to Tiny Show and Tell Us, a bonus episode from Tiny Matters, a production of the American Chemical Society.
Sam Jones: To be featured in a future episode, send us an email with your Tiny Show and Tell Us at tinymatters@acs.org, or click the Google form link in this episode's description. See you next time.
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