 Thank you for tuning in to Davis Media Access TV. I'm Lynn Weaver and our topic today is to learn more about our immune system and the brain. New evidence shows that the immune system and the brain are in direct connection with one another and they also impact one another as we go along. And this new understanding will hopefully result in a new understanding of diseases such as multiple sclerosis or Alzheimer or schizophrenia. And to learn more about how they occur and hopefully find cures for them. We all know that when our immune system is not functioning as it should, we all get sick but we don't quite know why. So here to help us to extrapolate all these complexities is my guest, Dr. Kimberly McAllister. Thank you so much for being here, taking the time to be with us. Dr. McAllister is an outstanding scientist of international reputation and has been recognized with a long list of very prestigious awards. She is, and I have to read because she has many title, a professor in the UC Davis departments of neurology in the School of Medicine and neurobiology, physiology and behavior in the College of Biological Sciences. And she's also the director of the Center for Neuroscience. I am. Wow. Thank you. Thank you for the opportunity to be here. Well, remember we're all lay people, so none of those complicated sentences. You mean like the list of the departmental names, right? Exactly. I read in one of your many bios that you love puzzles. I do. And is the brain a complicated enough puzzle for you? Oh, yes. Yes. You know, the brain is the most complicated thing in our entire universe and in anything that we can comprehend. And even understanding and studying just a tiny piece of it is so challenging. It's exciting. It's what makes us who we are, but we don't know very much about it. Well, that's interesting. Is there any particular aspect of the puzzle that you are interested in? I know you're interested in the immunity and immune system, but is there anything that first fascinated you? Yes. It's just a fundamental curiosity about what makes us who we are. Yes. The fact that in development our brains are nothing and in little babies in the womb and then they grow, the brain grows this very complicated structure. It makes all these connections and then it allows us to develop and become who we are. Each has individuals and it develops differently. And one of the most amazing aspects of brain development is that it's not just our genes that impact our brain development. It's our experiences. Fascinating. Fascinating. Well, we all want to know what is the immune system and what does it do, right? Well, that's also a complicated question, but we all have a sense for what our immune system is, right? We know that we need our immune system to fight off infection. And so our bodies have lots of different ways to do that. They're barriers, they're different cell types. And generally what happens is that when we have a cut, when our barriers are breached, we have a whole series of cascaded events that happens that causes cells to come into that site. You have some inflammation, which we all know, it's where it gets red and warm to the touch. But over time, you end up healing that wound. And our immune system is absolutely critical for that. We also have aspects of our immune system that fights off viral infection and bacterial infection in science. And I'm going to get back to that in just a moment because that's really very interesting. Now, tell me why do neuroscientists like yourself care about our immune system? Right. What's interesting is that when you're trained to become a neuroscientist, somebody that studies the brain, you learn so much about brain anatomy and about how the different cells in the brain work and how it's all connected. And that's difficult enough. But only recently have we started to realize that the brain isn't just completely separated from the rest of the body. In fact, it's influenced by it. And that sounds really silly from the outside of neuroscience that we didn't realize that. But in our brains, we have what's called a blood-brain barrier. And so there's a series of structures that surround your brain that prevents infections in the body from entering the brain. And so that allows us to function even if we get injured in elsewhere in our bodies. Even if we have peripheral information. That's right. And so for many, many years, it was thought that the immune system didn't interact with the brain because of that barrier. But about 20 years ago, there was one of my scientific idols, Carla Schatz, who's at Stanford. And she discovered that immune molecules are actually present on cells in the brain. And we've since gone on to discover that some of the signals from our immune system, from immune activation during infection, that they can cross the brain barrier during brain development and alter the development of our brains. And one example of this is you're studying a very important case, and that would be susceptible pregnant mothers who are susceptible to inflammation, viral inflammation, and can affect how the child, the unborn child's brain develops. And that can lead to what? That's right. So it's been known for a number of years that exposure to a wide range of viruses, including influenza, increases the incidence of a number of psychiatric disorders in offspring. And so one of the first ways that this was realized was by looking to see whether there were increases in the rates of autism or schizophrenia after pandemics. Oh, yes. And so you have to look at numbers of years later after the pandemic because it's the exposure of the fetus in the womb to something about those maternal infections that then was causing an increase in the incidence of a wide range of psychiatric illnesses. And so this has been studied for the most part by schizophrenia and autism, but there are also links to depression and to neurodegenerative diseases like Alzheimer's disease. So if I understand correctly what some of these dysfunctions, if you like, like depression, for example, malfunction, I should say, are not necessarily genetic. Well, so we know that a number of these diseases have both genetic components and environmental components. So we know, for instance, that autism and schizophrenia both are highly heritable, but there is also a strong role for the environment. And epidemiology or studies that look at the incidence of disease have really shown this strong link between the maternal infection and these diseases. But we don't know why. And so this discovery that immune molecules are present in the brain gave us the idea that maybe the mom's immune response, all of those signals and chemicals that get released in her body to fight off infection, that those might cross into the brain of the baby as it's developing and alter the structure of cells in the brain and the development of that brain that could then predispose the offspring to getting to getting these different diseases. Fascinating. Also, it's scary. It's very scary. And it's really important to realize that most infections, when you're a mom, oftentimes you will get exposed to a virus and most pregnancies don't end up with kids with psychiatric illness. Yes. But so one of the most important things in this field is to see if we can understand why some pregnancies are susceptible and most other pregnancies are resilient. Because if we can determine and identify which ones are susceptible, then we can treat the moms so that their offspring don't have that in the stress. Absolutely. And that is wonderful. Let's... There's something, I'm going to ask you an in-n-n question, and there's... Do other people who don't have immune systems, are these the babies who are in bubbles and in those bells that cannot live in oxygen like we do? Well, so I'm not sure exactly what you're talking about, but there are definitely... I'm not surprised. No, but there... I mean, we hear about this, right? And I don't have direct experience with that, but there are many, many people that are born with different levels of intensity of autoimmune diseases. Some of them can't fight off any infections, right? And these are severe immunodeficiencies. I think that's probably what you're referring to. And these are kids that kind of have to be kept away from infection in this bubble that you're talking about. That's right. Yes. And it's known, so a lot of... There's not a lot of people with this, but for the group of people that have this, it is known that their brain development is a little bit different than is typical and that that can lead to some behavioral proclivities, but there are just differences in behaviors, right? I see. And a lot of these psychological diseases we call them, they're things that are advantageous to having them and they're other things that are not, right? And so just talking about them as negative is not... They're a part of all of our lives, pretty much, with the incidents. That's a very good point that you're making. Now, I often read that if your immune system is somehow impacted by disease, by a virus infection, you may, one, may have diminished memory, diminished capability of learning. Is that a scientific fact? So it's hard to study because humans are really variable and the things that we do in terms of what we're exposed to, whether we take medication, whether we have disease, whether we smoke, those things can actually change the integrity of our blood-brain barrier. And so for some people, this can have an effect on their ability to fight infection and if they get sicker and their blood-brain barrier allows for signals to come through, that can then actually alter memory, learning in memory, it can alter mood. And we're just beginning to understand how it does that. Oh. They're these little proteins that are on the surface of your cells that are important for cells in the brain to talk to each other. That's how information flows. You're not talking about the neurons. I'm talking to the neurons of the brain cells and the connections between the neurons are called synapses. Yes. Good. Yes. And they're these really incredible molecular machines that are made up of thousands of different proteins, but what we've discovered in my own lab and in others in the world is that immune molecules, so molecules that we thought only mediated the immune response in our bodies, they're actually found at these connections. And so if the blood-brain barrier is compromised in any way for a number of reasons, those immune signaling molecules that usually are kept out that just fight infection can then enter into the brain and alter information flow across neurons because of altering those immune proteins. How extraordinary. It's really remarkable, nobody was expecting this. I could listen to you for about, I don't know, a whole week without getting tired. But I do want to ask, you're the director of the Center for Neuroscience at UC Davis. It's a big responsibility and you oversee many labs and so on. What would you say is the overall goal? I know the overall goal is to find the truth, the scientific truth. Beyond that, there must be a human aspect. Oh, there is. I'm not saying that scientists are not human. Oh, no, no, no. Yeah, well, and especially neuroscientists, so we want to understand how the brain works and we want to understand how it works for a number of different reasons. Yes. We want to understand how it makes us who we are. We want to develop new treatments and therapies and cures even for the wide range of brain diseases that affect just about all of us in our families. And we want to develop the next generation technologies that are really changing the world. So artificial intelligence is something that we all hear about in machine learning. We even have it in our phones that we all use every day. Those algorithms that run that artificial intelligence are based on how we understand information transfer in the brain from 30 years ago. Now when we understand it's so much better, we're developing new algorithms that are really going to drive technology development. So the overall idea is that we want to understand how the brain works so that we can use that knowledge to improve people's lives. Oh, this is wonderful. I'm afraid our time is up. It went very, very quickly. Yeah. Dr. Kimberly McAllister, thank you so much for being here. And I hope that we'll have a sequel to this. And for all of you, thank you for watching. And if you've liked this program, you can go on to our website, DCTV, davismedia.org, and check out some of our other programs. We have very interesting topics and wonderful guests. So please do check us out. Thank you again from all of us here at Davies Media Access. See you next time.