Brain Health: What happens when things go wrong?

Ever wondered what makes your brain so incredibly complex, or what happens when things go wrong? Join us for this tiny expedition as we demystify brain health and disease, breaking down the intricate cellular makeup of the brain and its vital functions. You’ll learn about the spectrum of brain diseases and disorders and how ongoing research is transforming our understanding of these often devastating diseases.

To go behind the scenes and learn more about this episode, visit “Brain Health: What happens when things go wrong?”

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Transcript

Chris Powell  00:05

Welcome to Season Six, Episode One of Tiny Expeditions. It's a brand new season, and for those of you who are listening to us, we want to let you know about a little bit of a change. You can still listen to us, don't worry, but we've made the jump to video. So once you're at your computer, if you're driving now, don't do it now. But once you're at your computer, you can go to YouTube and search up HudsonAlpha, and then within that HudsonAlpha channel, you'll see the Tiny Expeditions podcast list, and we are there, and you can watch us as well as listen. So we're excited about that change, but for this episode, we need to get rolling, and to do that, you need to know who we are. My name is Chris. I'm going to be your storytelling guide for this episode.

Sarah Sharman  00:48

And I'm Dr. Sarah Sharman here to help you understand the science. This season is all about the brain. We'll talk about what's a healthy brain, what can go wrong with your brain, and how scientists are learning everything they can about the brain to solve some of our world's most insidious brain diseases and disorders.

Chris Powell  01:04

And we've got a lot of great guests lined up for this season. But for today, we are talking to two HudsonAlpha researchers. They're gonna help us get a baseline understanding of what our brains do, why our brains are so important. I think most of us would say they are indeed important, and what can go wrong with them throughout our lifespan. And then we're also gonna hear a first-hand story that really emphasizes what happens when things do go wrong and why this research is so important. But first, let's talk about the brain.

Sarah Sharman  01:34

The brain. The brain is the most important organ in the human body. Zombies eat them. 

Chris Powell  01:41

Okay, wasn't prepared for that, but sure. I mean, at least movies tell us that we need to make sure we specify: science has not proven that zombies eat brains.

Sarah Sharman  01:50

That is true, and we missed our mark for that one for season five. But we are in season six, and we're talking about the brain, and in all reality, it is the central organ of the nervous system in most vertebrates and invertebrates.

Chris Powell  02:03

Excellent, and it does a whole lot of really cool stuff that most of us just take for granted we don't even think about on a daily basis, like what? What does the brain help us do? 

Sarah Sharman  02:12

So the brain functions as the command and control center for the body. So that includes a ton of things. One example would be processing sensory information. So when you touch something that's hot, your finger sends signals up to your brain to tell you pull your hand back, stop touching that.

Chris Powell  02:29

Okay, so it's helping us process and interpret the world around us. Yes, generating motor commands. What does that mean?

Sarah Sharman  02:36

So that would mean, as you had your hand on the hot object, it would tell your hand to pull back, but that has to tell your muscles that they need to make that movement. 

Chris Powell  02:45

Okay, so an interconnectedness of the rest of the body here and it also regulates physiological processes. So what do we mean by that? 

Sarah Sharman  02:55

That means when you're panicking because your hand is on that hot object, and your breathing gets really high your body, I mean, your brain tells you slow down, you're going to be okay, control your breathing, your heart rate, things like that.

Chris Powell  03:06

Or in my case, when my brain tells me you're hungry, which seems to be all the time, or that you need to go to sleep, like that's what my brain says, Yes, exactly, okay. And then there's also the higher cognitive functions, and this is what we often think of when we think of the brain, right? So what are we saying when we say the higher cognitive functions?

Sarah Sharman  03:26

So really enabling our thought, learning, memory, and language. So when you're trying to talk to me about philosophy, that's using your higher thoughts. 

Chris Powell  03:35

So this is when we tell somebody to use your brain. This is usually what we're talking about in this case, right? Yeah. Like, put things together, put two and two together, to use the phrase problem solving that all happens here, but then also orchestrating emotions and personality that all happen in the brain as well. What is that?

Sarah Sharman  03:55

Yep, so it really influences your mood, your social behavior and just individual characteristics that make you who you are. Okay?

Chris Powell  04:03

So our individuality is, in part, shaped by this, right, and also helps us process the world through our emotions. Excellent. So I think we can all agree that the brain is incredibly important, but it's incredibly complex.  

Sarah Sharman  04:19

To help us understand that complexity, let's jump right into one of our interviews with senior scientist, Dr Jacob Loupe here at HudsonAlpha.

Jacob Loupe  04:28

Part of what makes the brain so complex is at a very basic level, it is composed of a lot of different things. So many organs of the body, they're made up of a few cell types, but there's a really predominant cell type that defines it. And in the brain, we may think about the nerves, and obviously, the nerves are kind of the star of the show there, because they're making these electrical impulses and sending those signals. But there are a lot of other cell types. You've got the nerves that are sending these long projections to other neurons and taking those signals. But it's like a wire. We always talk about it like wires because we're sitting on like signal, but you have to insulate those wires. And we have what we call oligodendrocytes. There's going to be some scientific terminology, we have to throw it out there, but these actually insulate those nerves, so that's cool. They have to have that function. But then you've also got a support structure of astrocytes that are connecting to those and helping to keep those cells healthy. And then you've got what we call microglia, and these are sort of your natural innate immune system in the brain. They're specific to the brain, and kind of help fight off potential infections or prune out any diseased or dying cells or bits, and help get rid of that and clear that. So what I like to tell people, especially when I go back and I'm talking to friends and family on a basic level, if you have anything in your body, on your body, it either is a cell or was made by a cell. So all this complex machinery in your brain that we like to, you know, make analogies to, you know, a microchip or a machine, anything like that. It's a bio machine. It's all made up of cells, and each one of those cells has a very specific function. And even to each one of those cells, there are subtypes of those cells, like neurons. Not all neurons are the same, and it changes on different parts what part of the brain you're talking about. 

Jacob Loupe  05:49

So the basic makeup of the brain is complex, but even for the regions that have that same makeup, they do very different things, because we know that there are parts of the brain that are very involved with higher intellectual thinking, decision making, but other ones that are responsible for that taking in sensory information, other ones that are dedicated for moving. And we have all of these folds and regions of the brain, and we know that if you have damage to one part of the brain, it affects one side of your body, one part of your body, what you can see, what you can hear. So it's interesting that it's so complex in its makeup, but also in its organization of that makeup. So it's really complex, and there's so much information that we know about it, just because of all the years of us studying the brain, but there's still so much more at a more and more granular level. The more you peel it back, the more complex it gets. So it's harder to understand it all, but hopefully, the technology is keeping up that we can study and go deeper and deeper, but the more and more we dig in, it just gets more and more complex. It's fractal, but it's cool.

Chris Powell  07:09

Let's push this in the direction of what happens when things go wrong. Okay, so what are we talking about? Let's define out, first off, some of the diseases or disorders that we're going to be talking about. I know you mentioned Huntington's before, but what are some of the most common that we most common that we would need to discuss?

 Jacob Loupe  07:31

Sure, I kind of break it into, I think, three groups I was thinking about before, so kind of early, mid, and late. So, neurodevelopment, things that affect you as you're growing up. So this could be things like intellectual disability, ADHD, things like that, that kind of, you can see them in younger individuals, like maybe there's something that's going on with their ability to learn, their ability to interact with other people, and there's clearly, there's some environmental aspects of that. There's genetic components to that. In fact, the balance between environment and genetics is just going to be huge for every disease, especially for brain health. 

Jacob Loupe  07:55

The one I talked about, sort of in the middle, as you're developing, these are more neuropsychiatric diseases, so something like schizophrenia or major depressive disorder or bipolar disorder. So these are ones where it might not have a physical representation, but it's truly something that's happening, you know, in someone's brain. It's, it's a real phenomenon, but it's just really hard for us to have the exact measurements of those. 

Jacob Loupe  08:18

And then late-stage neurodegenerative disease. So it is a disease that, as you get older, you actually can measure, so you can actually see the cells or regions of the brain starting to deteriorate. Now, as we get older, all parts of our body kind of start to deteriorate. And even what we would call a normal, healthy person, even as they reach 90, 100 years old, like things kind of start to atrophy. And the brain’s no different. But there are some individuals who were way before that, 100-year-olds, like in their 50s and 60s, different parts of their brain, or maybe starting to struggle, or maybe even starting to become impaired, or even just disappear altogether.

Chris Powell  08:52

Sarah, I feel like we may need to pause here for just a minute and maybe define some terms. We've talked about some broad classifications, like neurodevelopmental, neurodegenerative, neuropsychiatric like, what exactly does that mean when we talk about those different classifications?

Sarah Sharman  09:07

Sure. So like Dr Loupe mentioned, there are really three main buckets that we can put these big brain disorders and diseases into. So, starting with neurodevelopmental diseases, these affect the way your brain develops in early life, they can cause problems with learning, socializing, and intellect, things like that, and we generally see these manifested first in babies and children. Secondly, we have neuropsychiatric diseases, and these happen when you have a change in your brain structure or chemistry that leads to issues with thinking, feeling and acting. These can be a little bit more abstract.  in their cause, but they include diseases like schizophrenia, major depressive disorder, bipolar disorder. Then the third main bucket is neurodegenerative diseases, where brain cells are slowly degenerating and dying. This can lead to problems with memory, mobility, and thinking. And these would be things you think of, like dementia, Alzheimer's, Parkinson's disease,

Chris Powell  10:05

In hearing that list, obviously, there's no wonder why Jacob before was talking about the complexity of the brain. I mean, that's a whole lot of ground that we've covered that is all happening inside of a single organ. 

Sarah Sharman  10:17

Oh, absolutely. And to make things more complicated, the cause of many. And many of these diseases and disorders are not well understood. I mean, we know a lot more than we did before, but we definitely don't know everything. What we do know, however, is that a lot of them have genetic influences, and that's why we're studying a lot of these here at HudsonAlpha. 

Chris Powell  10:36

And while you and I don't know all of this, we do know some people. We know some people who have a much better understanding, so let's talk to one of those right now. Let's talk to Dr. Rick Myers.

Sarah Sharman  10:48

Well, I know there are different ways that genetics play a role in neurodegenerative and even neurodevelopmental diseases. Can you kind of touch on that, like what's happening when we say that your a gene is messed up in these diseases?

Rick Myers  11:02

So first of all, it's important to understand that genes play a role in everything that happens in all life, certainly in humans. In many cases, but not all, there can be a mutation or a mistake in a single gene out of our entire genome that ends up causing the disease. The majority, however, are not single genes. They're often multiple genes that contribute to it in combination with the environment. And I know we'll talk about that some, because it's not all just the genes. What's remarkable is out of all the genes that we have, and out of the 3 billion base pairs of DNA of that we have in our genomes, for our DNA, you can make one single change that ends up causing a devastating disease, not just in brain, but in other systems as well. And I found that so fascinating, because it shows you how important this orchestration of all of our genes together in really all of our cells, how important that is for sort of development, how we become what we are, and then what goes wrong when there's a mistake in one of those genes that encodes for a protein.

Chris Powell  12:32

You alluded to this a moment ago, but can you tell us when it comes to brain health, how much of this is influenced by genetics, and then how much of it is environment?

Rick Myers  12:41

So there has been, I don't know how long the argument for nature versus nurture has been around, and it's just a myth. There's nothing that works in isolation. Even when you have a devastating mutation in a single gene, the environment can play a big role in what happens, the age of onset, and certainly the progression of the symptoms. And the environment can be all sorts of things. A treatment with a drug is an environmental contribution. And actually, so far, we haven't had any completely reverse, any neurodegenerative or even neuropsychiatric or neurodevelopmental disorders, but we have some that actually make a difference. So that combination is really important. Another way to think about environment, and this has been a really interesting thing that has happened really fairly recently. Let's take Alzheimer's disease as one example, where it turns out that there are behavioral and dietary and other things that can contribute to making the symptoms less severe. Don't take that the wrong way, that oh, you take some magic elixir or some magic diet, and then you're okay. But the fact is we clearly have a genetic contribution, maybe multiple genes, or maybe even a single gene, in some of the cases, but clearly, you can mitigate that somewhat with some things like various behaviors. You'll hear more about this with our work at HudsonAlpha, where we're Nick Cochran, leading this team to study how a combination of environmental and sort of preventative things can maybe help as well. 

Rick Myers  14:38

One of the things that I love about this research, and watching the advances being made, is that we're understanding more and more about how the brain and the nervous system work, even without disease. And that's actually critical. If you don't know what the normal function is, it's difficult to think about how you might treat it if you don't really understand how it works normally. The advances being made in that, and it's essentially neurobiology, genetics and genomics are playing a huge role in that, but so is imaging and many, many other studies. And it's that combination that I find the most exciting. When I first started working on brain related diseases and normal function, I honestly didn't think we would be making advances to lead to treatments and prevention and prediction of whether you're going to get a particular disease in my lifetime. It just seemed so far away because it's such a complex organ, and biology is complicated anyway, and the fact that so much basic and applied research is being done in combination has just led to so many advances. I just can't wait to see what's going to happen every year, really every month, there are new developments that make it really exciting.

Chris Powell  15:59

So, though we're talking about advances in research in brain diseases and disorders, for those who are affected by these, it may seem like these advances aren't coming quickly enough, right? We want those to come even quicker. And one thing that we've learned in crafting this episode is that there are so many people who are affected by these diseases and disorders. And one thing that is very interesting to me is the dynamic that occurs when someone is personally affected by a disease or disorder of the brain, and they're also in the lab studying this. 

Rick Myers  16:32

The other thing is that these are really common. My mother died from pancreatic cancer, but she had Alzheimer's disease before she came up with cancer, and it's really hard to watch that happen, and almost at the same time. But for more years than that, my father had Parkinson's disease and eventually succumbed to the symptoms of that. This very common story, you'll hear this from almost everybody's touched by it in some way or another, either directly in their family or at least with friends.

Sarah Sharman  17:04

Rick's personal connections to devastating brain diseases are just one out of millions of stories. Throughout this season, we want to bring you the science, but also the personal connections behind these tough diseases. For this episode, we sat down with another individual whose life has been affected by one of these diseases. Marc Bendickson, the former CEO and Chairman of the Board of Dianetics and a member of the Hudson Alpha Foundation. Marc's wife, Sheryl, lived with Parkinson's disease for nearly two decades. 

Chris Powell  17:32

Can you tell us how your family has been affected by neurodegenerative disease? 

Marc Bendickson  17:37

Well, it's actually been affected on probably two different levels. I mean, my personal relationship was affected very severely. My wife and I, of 55 years of marriage, Parkinson's brought that to an end and sort of interrupted our golden years of retirement. So, from one respect, it was a very huge impact on me personally, on my children, who were missing their mom and grandmom. I'd say on another level, we adapted our family to live with a patient with Parkinson's, and life went on pretty much as usual for the first several years.

Sarah Sharman  18:22

So, can you tell us what that was like when you first learned your wife had Parkinson's? Did she have a family history, or anything? Or was this just kind of out of the blue?

Marc Bendickson  18:31

It was really out of the blue. I knew one person in my life who had ever had Parkinson's, it was an older gentleman. And my wife knew she had one aunt that had it. She lived in Washington, DC, I believe, and she had Parkinson's. But we didn't know anybody who had Parkinson's and hadn't really thought about it. We sort of discovered it just one night in bed. She was lying there, and her leg was really twitching and in a lot of pain, and she knew something was wrong. That's when she went to doctors, and she didn't have much hand tremors for that, but they did verify that it looks like she probably had Parkinson's at that point. That was our first discovery, but it was kind of a shock to our system. 

Chris Powell  19:18

So what was she like both before and during the onset of disease?

Marc Bendickson  19:27

Well, she was very bright. She did much better in school than I did, and was extremely active. She just enjoyed everything she did. She enjoyed entertaining dinner groups. We were in dinner clubs, and she enjoyed cooking, a great cook. She was a teacher by training. She enjoyed teaching kids. She loved babysitting grandkids. She was so busy she wore me out. She loved traveling. Would travel with all kinds of groups, set up our retreats, and our vacations. A very active person and had a strong disposition to handle whatever she was dealt.

Chris Powell  20:11

Was Parkinson's on your radar at all before this diagnosis?

Marc Bendickson  20:16

No, never. I had heard of it only. I didn't even know what the name was, but I remember this one gentleman that my dad knew that had the shakes and the tremors, and I learned later that was Parkinson's so I didn't even know what the name was, probably.

Sarah Sharman  20:31

So, along those same lines, we talk a lot about the people who are suffering from these diseases, and I don't think we talk as much about the families who are caring for them. Is there anything you would say to others who are caretakers to someone diagnosed with a neurodegenerative disease? Any advice or helpful words?

Marc Bendickson  20:53

Well, certainly, I think the thing to do is not to let it totally shut your life down. You've got to go on living, doing the majority of the things that you enjoy doing. And I think the families need to be accommodating. They need to sort of adapt how you do things, but not stop doing things. And I believe my family did a great job, my children, my grandchildren, just really embraced that whole concept. It was hard on my daughter, for sure, my son, I mean, they knew their mom was having a lot of pain and dealing with that, but I think you have to embrace that pain. And know there's times she's going to end up in ER and have falls that are serious and stuff like that. She had a couple falls that were bad, she had a traumatic brain injury out of one of them. 

Chris Powell  21:47

Let's, let's do a little thought experiment. Okay, so let's say it's five years from now, and you walk outside and you're picking up the newspaper, which I guess is a lost image. People have newspapers delivered to their houses anymore, but let's say you have a newspaper delivered to your house and there's a headline about the next great advancement that's happened, and specifically in Parkinson's, what does that headline say to you?

Marc Bendickson  22:15

I would love to see, well, first of all, I'd love to see it say we have a definite marker that tells you whether or not you've got Parkinson's. I think it's important for everybody to know what disease they've got and what they're dealing with. So that'd be the first thing. Then it'd be great to have it so that we actually can pinpoint this disease, what's causing it, we can target medications that will counteract just that disease and not broader aspects. I think targeting disease is one of the great things that we're doing here at HudsonAlpha, so that dosages can be appropriate in hitting the right areas. I think if we could get down to that, then you can get closer and closer to dealing with and maybe ending Parkinson's disease.

Sarah Sharman  23:07

It's all like super complicated biology, as you've kind of laid it out, and there are a lot of things at play, like genetics and environment, and sometimes more than one gene, but I think we are making really good progress. Is there anything you're exceptionally hopeful for in the field of neurodegenerative research?

Jacob Loupe  23:27

Yes, we're definitely hopeful. Because we're seeing innovations, even in our lab, every day, every year. I think we're getting a little bit closer and closer to being able to better understand these, and also, one of the things is that being more hopeful is also that we're shining light on some of these diseases. I think maybe that's on the taking a step back from the biology, just being able to maybe get rid of some of the stigma around some of these diseases. You know, someone you know, can't take care of themselves anymore, their brains going, it can be a very uncomfortable discussion to have and to realize, but getting more and more people to say, look, this isn't some fault in character or fault in this individual. It's just a biology process. This is a disease, a disorder, and being able to collaborate or participate in studies, talk to your physicians, talk to your family about it, just getting people generally aware and why it's important to invest and participate in research like this. So that's what gives me hope, is people being able to study basic human biology of the brain earlier and earlier, in a more defined way, is giving us that base information that we can build off of. So I think a lot of people want that home run therapy, and they want it now. They wanted it 10 years ago, but we're still building towards it, and that's why you know research and investing in research is so important, because it just takes. It takes a long time, but once you've built that foundation, once we know that this cell type is involved with another one, I said, we don't have to keep researching it. It's out there, and then the next person can take and then the next person can take it.

Chris Powell  24:57

So as we close out this first episode of season six, let's do something a little bit different. Sarah, let's take just a moment and let's recap. Let's do a TLDR, right? So if somebody tuned out for a minute, let's catch everybody up. What all have we talked about? Or, I guess, more importantly, like what stuck out to you as kind of being some of the more important things that we need to take on from this episode?

Sarah Sharman  25:21

Sure. So I think one theme that kind of strung throughout this episode was complexity, and I mean that on a few levels, like the complexity, because there are so many types of diseases and disorders of the brain. As Jacob said, there are so many different cell types and tissues in your brain, so the brain itself is complex. How complicated research is itself. And then another layer to that...

Chris Powell  25:45

Let me jump in here, because that complexity is going to be great for us, because it gives us a full season of things to talk about. So we've got, we've got a lot ahead of us here. Very true. Sorry, go ahead.

Sarah Sharman  25:56

And then the other thing is just the multifactorial nature. And what I mean by that is how many things we think are helping to cause these diseases. So is it genetics? Is it in the environment? Is it a combination of both? 

Chris Powell  26:09

Yeah, and one of the things that stuck out to me was actually from what Jacob was telling us about, and that was towards the end, when he was talking about the hope and how we need to be careful to start thinking of the stigma that's around a lot of these diseases and disorders, and being able to name them and to name them for what they are, as biological processes and not have that stigma attached to it. And the other thing that really jumped out to me is the fact that so many people are affected, and we haven't even gotten into like the heavy, I mean, not the heavy stuff, yhis is obviously heavy. But we haven't gotten into the multiplicity of disorders and diseases that we will throughout the rest of the season, and already we've got lots of stories of people who have been affected by these diseases and disorders, so that really stuck out to me. But along with that, I think we could probably both say the hope.

Sarah Sharman  27:01

Oh, absolutely on many, many different levels, just from research progress, progress with treatments, our increase in knowledge of these diseases. Yeah, it's definitely a good feel at the end.

Chris Powell  27:14

And with that hope, I think it we should also have this sense of gratitude with that, you know, thankful that people are willing to dedicate their lives to researching this, whether it be through family connections or personal connections or just something interested them, you know, putting the brain power to use for good. That's right, that brain power. So with that, we'll say thank you for joining us on this special debut episode of season six, and the debut episode with video too. Hopefully, you enjoy that. Let us know in the comments if you did, and we'll, you know, look at where we go from here. But we hope you've learned a lot about your brain and specifically the research that's being done by these brilliant researchers in brain health.

Sarah Sharman  27:57

So this episode, we really hoped to lay the basis for the rest of the season. In the next episode, we're going to jump into one of those disease categories and look into neurodevelopmental diseases and what researchers are doing to help diagnose these earlier and hopefully treat some of them

Chris Powell  28:13

That'll be next time. But right now, Tiny Expeditions is a podcast about genetics, DNA, and inheritance, from the HudsonAlpha Institute for Biotechnology. We're a nonprofit research institution in Huntsville, Alabama, with a unique mission.

Sarah Sharman  28:27

We bring together scientists and companies to develop and apply genomic advances to make a better world. That's everything from brain research to agriculture for a changing climate.

Chris Powell  28:37

If you enjoyed this episode, swing by your favorite podcast app or here on YouTube, and hit that subscribe button, and while you're there, consider leaving us a review or a comment. It really helps us spread the knowledge and to understand where you're at.  

Sarah Sharman  28:50

Thanks for joining us.