Selected Podcast
Anxiety and Asthma: Understanding Communication between Brain and Airway
Asthma attacks account for nearly one-third of all asthma deaths. Anxiety is a common comorbidity in asthma that is associated with poorer asthma control and decreased quality of life. Despite links between asthma attacks and anxiety, there have been few studies in the asthma field of the amygdala, the brain region that initiates anxiety. Dr. Leah Reznikov, an associate professor of physiological sciences, discusses how her research aims to tackle that considerable gab with the goal of developing new approaches to treat asthma and reduce patient deaths.
Featuring:
Learn more about Leah Reznikov, Ph.D.
Leah Reznikov, Ph.D.
Leah Reznikov, Ph.D. is an Associate professor of physiological sciences, UF College of Veterinary Medicine.Learn more about Leah Reznikov, Ph.D.
Transcription:
Melanie Cole (Host): Welcome to UF Vet Med Voice with the University of Florida College of Veterinary Medicine. I'm Melanie Cole. And joining me today is Dr. Leah Reznikov. She's an Associate Professor of Physiological Sciences at the University of Florida College of Veterinary Medicine, and she's here to tell us about anxiety and asthma, understanding that communication between brain and airway.
Dr. Reznikov, it's such a pleasure and this is such an interesting topic. So, we know that asthma attacks account for nearly one-third of all asthma deaths. And anxiety, understandably, is a common comorbidity in asthma that's associated with poor asthma control and decreased quality of life. Can you tell us as we start this podcast what we know about the link between asthma attacks and anxiety and how that goes together?
Dr Leah Reznikov: So, surprisingly, we know very little about it. So, what has been reported over the decades is that individuals who have anxiety and asthma tend to have poor asthma control. And there's been a lot of interest in this over the years. And recently, what people have discovered is that the asthma attack or the process of an asthma attack can actually acutely activate the center in the brain that's responsible for generating anxiety, so the amygdala. And so really, my laboratory is focused on trying to understand how does the condition of asthma cause the amygdala become activated, so the fear center.
On the other hand, we're also interested in trying to understand what if your amygdala is different in activity? Does that then set you up to have asthma or does that mean if you have asthma you'll have worse symptoms? So, really I would say it's an open field, but there are several of us that are trying to understand that connection.
Melanie Cole (Host): Well, it certainly can go back and forth as you just described, pretty easily. And as this has received limited attention in the asthma field despite studies where we're looking at what you were just describing, can you tell us about the work being conducted in your lab that aims to understand that bidirectional communication between the amygdala and the airway, and how that influences airway physiology and pathophysiology, and especially in that context of asthma. This is so interesting. Tell us about what you're doing.
Dr Leah Reznikov: Yeah, absolutely. So, we are funded extramurally to basically investigate that question you just described. So, what is the bidirectional communication between the amygdala and the brain and the airway? And we're approaching this in several different ways.
So, one of the first things we're doing is we're just in a normal setting in experimental model systems. We are stimulating the amygdala. Now, the amygdala is complex. I'm simplifying it here, but the amygdala is actually a complex structure consisting of multiple different nuclei within a single structure. So, we are in my laboratory focused on the most upstream part of the amygdala that serves as one of the key areas that processes censoring information. And what we're doing is we're acutely stimulating that portion of the amygdala and asking, "What does it do to the airway physiology?"
And the way we test airway physiology in my lab is very simple. We have basically a ventilator that's specialized for experimental model systems. And then, we can, while we are stimulating the amygdala, see the effect on the airway physiology. So, that's one way which we're trying to understand this connection.
Now, as you can imagine, if you are an individual with anxiety, typically the idea is that the amygdala may be overactive. And so, one thing we're doing to understand that connection then is repeatedly stimulate the amygdala over a course of days and then determine what does that do to the airway physiology using the same methods, but we're also going to try to see if we can mimic features of asthma just simply by repeatedly stimulating a specific region of the amygdala. So, those are some of main focuses in the lab for understanding how the amygdala is communicating with the airway.
On the other hand, we're also going to take an experimental model system in which we induce asthma. And then, we're asking, "What does that asthma do to the amygdala?" And so, ways that we're addressing that is we're looking at structural and neurochemical remodeling of the amygdala in the context of asthma. We also have some great collaborators here that have allowed us to do MRI, so looking at brain activity in our experimental models that have asthma. And I can tell you that we have now completed a data set in which we're identifying sustained long-term changes in brain activity in response to asthma. And those brain regions that are showing sustained changes are downstream of the amygdala, suggesting that again the amygdala may be a key controller that modulates airway function.
Melanie Cole (Host): Wow, this is fascinating. Dr. Reznikov, so as you're working to develop new approaches to treat asthma and reduce patient deaths, as I understand it, you're using multidisciplinary approaches to answer some of these questions. Tell us a little bit about how that works.
Dr Leah Reznikov: What I really focused on was how we're measuring airway physiology. But asthma is really complex, and so the airway physiology can be affected negatively through multiple means. So for example, maybe you have exaggerated airway narrowing. This is termed airway hyperactivity. And what happens is the airway narrows in an exaggerated fashion to any sort of stimuli, and this would not happen in an individual who doesn't have asthma. So, the reason that's important is because if your airway is more narrow, you can imagine that makes it more difficult to breathe. So, when we measure airway physiology with our specialized ventilator, we're really focused just on sort of the airway narrowing aspect. But asthma also is involving inflammation. And so, we can say inflammation through a variety of different techniques. Typically, we're looking at some of the main known players that induce symptoms of allergic asthma, so IL-13, IL-4.
And then, we're also looking at, which is a significant interest in my lab, the production of mucus. So, excessive mucus is a hallmark feature of a number of different airway diseases. But in asthma, it is a sort of hallmark trait, if you will, that you can see that causes a lot of problems. And again, part of the reason it causes problems because it clogs up the airway and that makes it difficult to breathe. So when we say we're studying this in a multidisciplinary approach, we're basically focusing on all three of the hallmark features of asthma, including mucus inflammation and airway hyperactivity.
Melanie Cole (Host): Wow. So tell us a little bit about, if you were to summarize what you think is going to come from this and if you were to look for the next maybe five years. Where do you see this going as far as your research, this whole multidisciplinary approach, and the models that you're using, where do you see it going? How do you envision it going from bench to bedside?
Dr Leah Reznikov: In an ideal world, we always like to think that what we're doing at the bench will translate to bedside. And so, that is what motivates me in my scientific endeavors is potentially impacting human health or animal health, however it plays out. But what ideally we'd like to arrive to is some sort of new therapeutic, whether that be a standalone or an adjunct. And during our investigations, one thing we like to try to do is repurpose drugs that have already been FDA approved. And I didn't mention it, but we're keenly interested in how ketamine could potentially serve as a useful bronchodilator or a useful adjunct therapy for individuals with asthma.
I know that sounds kind of like it came out of left field, but the idea is that glutamate, which is a molecule that ketamine modifies, is really important for amygdala function. And we know now recently that there have been approved mixtures of ketamine that you can deliver intranasally. So, we're thinking that this could be almost like an adjunct rescue inhaler that's very overstating of what my big picture goal is. We don't have evidence that that'll happen, so I just want to make sure I put a little bit of caveat on that. But ideally, what we'd like to do is identify new therapeutics and, again, we're sort of looking towards ketamine as a potential for that.
Melanie Cole (Host): That's so cool, Dr. Reznikov. And I hope you'll join us again as things update and as you learn more because this is such an interesting topic and great work that you're doing there at your lab. So, thank you again for joining us. And for more information about the UF College of Veterinary Medicine, please visit vetmed.ufl.edu/ufachievers. And to listen to more podcasts from the experts at the University of Florida College of Veterinary Medicine, please visit vetmed.ufl.edu. That concludes today's episode of UF Vet Med Voice, brought to you by the University of Florida College of Veterinary Medicine, advancing animal, human and environmental health. I'm Melanie Cole.
Melanie Cole (Host): Welcome to UF Vet Med Voice with the University of Florida College of Veterinary Medicine. I'm Melanie Cole. And joining me today is Dr. Leah Reznikov. She's an Associate Professor of Physiological Sciences at the University of Florida College of Veterinary Medicine, and she's here to tell us about anxiety and asthma, understanding that communication between brain and airway.
Dr. Reznikov, it's such a pleasure and this is such an interesting topic. So, we know that asthma attacks account for nearly one-third of all asthma deaths. And anxiety, understandably, is a common comorbidity in asthma that's associated with poor asthma control and decreased quality of life. Can you tell us as we start this podcast what we know about the link between asthma attacks and anxiety and how that goes together?
Dr Leah Reznikov: So, surprisingly, we know very little about it. So, what has been reported over the decades is that individuals who have anxiety and asthma tend to have poor asthma control. And there's been a lot of interest in this over the years. And recently, what people have discovered is that the asthma attack or the process of an asthma attack can actually acutely activate the center in the brain that's responsible for generating anxiety, so the amygdala. And so really, my laboratory is focused on trying to understand how does the condition of asthma cause the amygdala become activated, so the fear center.
On the other hand, we're also interested in trying to understand what if your amygdala is different in activity? Does that then set you up to have asthma or does that mean if you have asthma you'll have worse symptoms? So, really I would say it's an open field, but there are several of us that are trying to understand that connection.
Melanie Cole (Host): Well, it certainly can go back and forth as you just described, pretty easily. And as this has received limited attention in the asthma field despite studies where we're looking at what you were just describing, can you tell us about the work being conducted in your lab that aims to understand that bidirectional communication between the amygdala and the airway, and how that influences airway physiology and pathophysiology, and especially in that context of asthma. This is so interesting. Tell us about what you're doing.
Dr Leah Reznikov: Yeah, absolutely. So, we are funded extramurally to basically investigate that question you just described. So, what is the bidirectional communication between the amygdala and the brain and the airway? And we're approaching this in several different ways.
So, one of the first things we're doing is we're just in a normal setting in experimental model systems. We are stimulating the amygdala. Now, the amygdala is complex. I'm simplifying it here, but the amygdala is actually a complex structure consisting of multiple different nuclei within a single structure. So, we are in my laboratory focused on the most upstream part of the amygdala that serves as one of the key areas that processes censoring information. And what we're doing is we're acutely stimulating that portion of the amygdala and asking, "What does it do to the airway physiology?"
And the way we test airway physiology in my lab is very simple. We have basically a ventilator that's specialized for experimental model systems. And then, we can, while we are stimulating the amygdala, see the effect on the airway physiology. So, that's one way which we're trying to understand this connection.
Now, as you can imagine, if you are an individual with anxiety, typically the idea is that the amygdala may be overactive. And so, one thing we're doing to understand that connection then is repeatedly stimulate the amygdala over a course of days and then determine what does that do to the airway physiology using the same methods, but we're also going to try to see if we can mimic features of asthma just simply by repeatedly stimulating a specific region of the amygdala. So, those are some of main focuses in the lab for understanding how the amygdala is communicating with the airway.
On the other hand, we're also going to take an experimental model system in which we induce asthma. And then, we're asking, "What does that asthma do to the amygdala?" And so, ways that we're addressing that is we're looking at structural and neurochemical remodeling of the amygdala in the context of asthma. We also have some great collaborators here that have allowed us to do MRI, so looking at brain activity in our experimental models that have asthma. And I can tell you that we have now completed a data set in which we're identifying sustained long-term changes in brain activity in response to asthma. And those brain regions that are showing sustained changes are downstream of the amygdala, suggesting that again the amygdala may be a key controller that modulates airway function.
Melanie Cole (Host): Wow, this is fascinating. Dr. Reznikov, so as you're working to develop new approaches to treat asthma and reduce patient deaths, as I understand it, you're using multidisciplinary approaches to answer some of these questions. Tell us a little bit about how that works.
Dr Leah Reznikov: What I really focused on was how we're measuring airway physiology. But asthma is really complex, and so the airway physiology can be affected negatively through multiple means. So for example, maybe you have exaggerated airway narrowing. This is termed airway hyperactivity. And what happens is the airway narrows in an exaggerated fashion to any sort of stimuli, and this would not happen in an individual who doesn't have asthma. So, the reason that's important is because if your airway is more narrow, you can imagine that makes it more difficult to breathe. So, when we measure airway physiology with our specialized ventilator, we're really focused just on sort of the airway narrowing aspect. But asthma also is involving inflammation. And so, we can say inflammation through a variety of different techniques. Typically, we're looking at some of the main known players that induce symptoms of allergic asthma, so IL-13, IL-4.
And then, we're also looking at, which is a significant interest in my lab, the production of mucus. So, excessive mucus is a hallmark feature of a number of different airway diseases. But in asthma, it is a sort of hallmark trait, if you will, that you can see that causes a lot of problems. And again, part of the reason it causes problems because it clogs up the airway and that makes it difficult to breathe. So when we say we're studying this in a multidisciplinary approach, we're basically focusing on all three of the hallmark features of asthma, including mucus inflammation and airway hyperactivity.
Melanie Cole (Host): Wow. So tell us a little bit about, if you were to summarize what you think is going to come from this and if you were to look for the next maybe five years. Where do you see this going as far as your research, this whole multidisciplinary approach, and the models that you're using, where do you see it going? How do you envision it going from bench to bedside?
Dr Leah Reznikov: In an ideal world, we always like to think that what we're doing at the bench will translate to bedside. And so, that is what motivates me in my scientific endeavors is potentially impacting human health or animal health, however it plays out. But what ideally we'd like to arrive to is some sort of new therapeutic, whether that be a standalone or an adjunct. And during our investigations, one thing we like to try to do is repurpose drugs that have already been FDA approved. And I didn't mention it, but we're keenly interested in how ketamine could potentially serve as a useful bronchodilator or a useful adjunct therapy for individuals with asthma.
I know that sounds kind of like it came out of left field, but the idea is that glutamate, which is a molecule that ketamine modifies, is really important for amygdala function. And we know now recently that there have been approved mixtures of ketamine that you can deliver intranasally. So, we're thinking that this could be almost like an adjunct rescue inhaler that's very overstating of what my big picture goal is. We don't have evidence that that'll happen, so I just want to make sure I put a little bit of caveat on that. But ideally, what we'd like to do is identify new therapeutics and, again, we're sort of looking towards ketamine as a potential for that.
Melanie Cole (Host): That's so cool, Dr. Reznikov. And I hope you'll join us again as things update and as you learn more because this is such an interesting topic and great work that you're doing there at your lab. So, thank you again for joining us. And for more information about the UF College of Veterinary Medicine, please visit vetmed.ufl.edu/ufachievers. And to listen to more podcasts from the experts at the University of Florida College of Veterinary Medicine, please visit vetmed.ufl.edu. That concludes today's episode of UF Vet Med Voice, brought to you by the University of Florida College of Veterinary Medicine, advancing animal, human and environmental health. I'm Melanie Cole.