Keeping Grey Matter Healthy – Metabolic Disorders and the Brain with Catrina Robinson, PhD

When you think about how to be more healthy, one of the things you might think about is your body weight. When our body weight is higher than what is considered healthy for our height, we might be described as overweight or obese and some common health issues come to mind when we think about being overweight: Type 2 diabetes, heart disease, and some cancers.

But body weight and related metabolic conditions like diabetes are also linked to our brain health and, in particular, our risk for Alzheimer's disease. With obesity at epidemic proportions, high economic costs of health-related issues, and an increasingly aging population, understanding the connection between obesity and brain health is critical. Thankfully, researchers are investigating obesity and cognitive decline and what might be done to protect our brains as we age.

Dr. Catrina Robinson is an Associate Professor in the Department of Neurology in the MUSC College of Medicine. Her research focuses on understanding the role of metabolic disorders (such as prediabetes, diabetes, and obesity) on brain health and aging, as well as understanding the pathways involved in developing novel therapeutic targets to improve brain health.

Read The Transcript

[00:00:07] Gwen Bouchie: From the Medical University of South Carolina, this is Science Never Sleeps where we explore the science, people, and stories behind the scenes of biomedical research happening at MUSC. I'm your host, Gwen Bouchie. When you think about how to be more healthy, one of the things you might think about is your body weight. When our body weight is higher than what is considered healthy for our height, we might be described as overweight or obese and some common health issues come to mind when we think about being overweight: Type 2 diabetes, heart disease, and some cancers. But body weight and related metabolic conditions like diabetes are also linked to our brain health and, in particular, our risk for Alzheimer's disease. With obesity at epidemic proportions, high economic costs of health-related issues, and an increasingly aging population, understanding the connection between obesity and brain health is critical. Thankfully, researchers are investigating obesity and cognitive decline and what might be done to protect our brains as we age.

In this episode of Science Never Sleeps, we're chatting with Dr. Catrina Robinson, an associate professor in the MUSC Department of Neurology, about her research to better understand the impact of metabolic disorders on both normal and pathological brain aging. Stay with us.

[00:01:38] Bouchie: Dr. Robinson, welcome to Science Never Sleeps.

[00:01:41] Catrina Robinson, PhD: Thank you. It's a pleasure to be here.

[00:01:44] Bouchie: I'd like to start today by asking you about your path to becoming a basic science researcher. What brought you to science and your particular interest in being in biomedical research?

[00:01:58] Robinson: So, I think my interest probably started really young. I grew up in a family where my grandmother had diabetes, stroke, and dementia. And also, my mother had breast cancer. So, seeing the health issues that were impacting my family, I always had lots of questions. I wanted to understand the why, why things were happening to their body and really trying to just understand what are some things that we can do to possibly make it better. So that was my initial dive into my interest in the sciences.

Also, I am from Tuskegee, Alabama, and my grandparents were part of the Tuskegee Syphilis Study and so there was a lot of talk always in my family about the study. And I was always curious about well, what happened to their bodies when they had syphilis? Like I was really curious about the process in general. And so that's how I knew that science was near and dear to my heart and I wanted to pursue a career in science. Starting out in college, the only way that I thought that I could, you know, have an impact in science was to be a medical doctor. So that was my goal was to go to medical school, get an MD. However, I started my journey in undergrad, struggled with a class, biochem, and had a tutor who was actually in graduate school pursuing a PhD. So, I started volunteering in a lab, literally washing dishes for the laboratory, and I fell in love with research. Started working in the laboratory, transitioned to a master's program, and ultimately ended up getting a PhD and I've never turned back ever since.

[00:03:40] Bouchie: And you mentioned that there was diabetes in your family and it's one of the things that you wanted to understand and as a researcher it's one of the areas that you are working in because you're working in metabolic disorders. Can you tell us a little bit about what metabolic disorders are and why research to understand them is so important?

[00:04:05] Robinson: Metabolic disorders are a group of disorders such as diabetes, insulin resistance, high cholesterol, hypertension, and these disorders ultimately can lead to changes within the body that impacts the brain and places it at risk for cognitive disorders or stroke later in life. So, my research focus is really trying to understand what is it about metabolic disorders and the changes that happen early on that ultimately has early changes in the brain.

[00:04:40] Bouchie: So, what contributes to some of these things in the body? You mentioned things like insulin resistance, hypertension, what are some of the things that we know contributes to this?

[00:04:52] Robinson: One interesting thing and one thing that I like to always show people when I talk about my research is if you look at the map of the U.S., and look at the incidence of diabetes, obesity, insulin resistance, any of those metabolic disorders, one thing you'll notice is that the Southeast has the highest percentage of all of these disorders. And so, when I think about the South and what's really great here is the food. So, is our Southern diet really driving some of these changes that we see or leading to the disorders that are here? And that's what my research is really focused on. I'm really focused on the high-fat diet and trying to recapitulate the Southern diet. And one thing that I can always remember that my grandmother taught me is that to make any vegetable taste great, you just add a little bit of pork fat. And so that's what we use in our diet in the lab is a high pork diet.

[00:05:49] Bouchie: That's really interesting. So, in your lab, you're using an animal model.

[00:05:53] Robinson: Yes, correct.

[00:05:55] Bouchie: And so, in your animal model, you're working with feeding them the same types of foods that humans are often eating that you believe are leading to these disorders

[00:06:09] Robinson: Yes, that's correct. So, we're feeding them a high-fat diet. It's actually 54% fat and I'm often asked, "Can I really consume 54% fat?" And yes, you can. It's really easy to do. If you forget breakfast in the morning, you stop at McDonald's and get a bacon, egg, and cheese biscuit and for lunch, perhaps you just get a Subway tuna, and for dinner, you just eat iceberg lettuce and ranch dressing. You've consumed 54% fat. So, it's pretty easy.

[00:06:38] Bouchie: Wow, that's incredible. What is the connection between diabetes and memory? So, you mentioned that this is something that you're particularly interested in your research. What is the connection there?

[00:06:47] Robinson: So, there is a link between individuals who have diabetes. They are at an increased risk for developing Alzheimer's later in life. So, this risk can go up to 80%. And so, what my research is focused on is really trying to understand why is that the case? What happens in diabetes that ultimately can lead to changes in the brain? So, when we think about diabetes, we're thinking about a peripheral disorder where you have high levels of glucose and your body just can't clear it to use it for energy and fuel and get it into the tissues, and so you have high levels of insulin so you end up with insulin resistance. But what we are interested in is how insulin and glucose, they're also important in the brain and they have different functions. Unlike your muscles, you don't need insulin to necessarily get glucose into the cells in the brain, but insulin plays a huge part in learning and memory. It has synaptic roles, it plays roles in inflammation, and insulin actually has to be transported from the bloodstream into the brain. And what happens in metabolic disorders such as obesity and diabetes is that you actually have a decrease in the transport of insulin so you have a deficiency of insulin in your brain. And so, our research is really focused on trying to understand if this deficiency is ultimately what connects diabetes to having memory disorders, and if we can increase insulin in the brain to ultimately improve memory function. The mechanism for diabetes and insulin both in the brain and in the body is fairly well researched.

[00:08:27] Bouchie: So, what you're looking at is how do we take that knowledge even further to understand how it impacts the brain or how it impacts memory and how to improve memory moving forward.

[00:08:41] Robinson: Correct. We know a lot about insulin in the bloodstream and the periphery, but what we don't know is how insulin actually is transported from the periphery to the brain. And there's not a lot of studies really trying to focus on is insulin perhaps a target for us where we can actually improve memory function or brain function in general by targeting insulin and increasing insulin levels.

[00:09:10] Bouchie: As we look at metabolic disorders, diabetes in particular, are there any groups that are more impacted than others when we look at this from a population health perspective?

[00:09:21] Robinson: Absolutely. There's a disparity when it comes to metabolic disorders. Diabetes, for instance. African Americans are more affected by diabetes, as well as other populations including Hispanics. They also are more disproportionately affected by diabetes as well. So, thinking about here in South Carolina, there is a disparity when it comes to looking at some of these metabolic disorders and it definitely needs to be an area that we should focus on to try to improve because ultimately, having diabetes can lead to dementia later in life, it can also be associated with increased risk for stroke. And so, if we could target disorders early on in the pathway-- So if we could target diabetes before it's a problem, then we can ultimately perhaps decrease the risk of some of these other disorders later in life.

[00:10:23] Bouchie: Do we see a connection in the impact between-- you mentioned the African American community being impacted-- do we see a connection between increased diabetes rates and then it also impacting disproportionately African Americans in Alzheimer's and other memory disorders?

[00:10:44] Robinson: Yes, that is also the case as well. African Americans are more disproportionately affected by Alzheimer's disease as well as stroke. One of the issues we also see with stroke is that when you look at the African American population, after stroke, they tend to have more impairment or longer term impairments related to stroke.

[00:11:08] Bouchie: And that seems like, particularly, a complex issue because there are lots of reasons why outcomes might not be what you would expect or outcomes would be a bit disproportionate in a particular community, correct?

[00:11:20] Robinson: Correct. It's actually a really great thought because we don't really know why that's the case. Actually, I was a part of a study that was funded by the American Heart Association, and this was an interdisciplinary project where we were really trying to understand why are African Americans more likely to have long term impairments after stroke? And this is when all things are considered equal. So, if you have equal socioeconomic status, equal education, equal access to care in terms of rehab, they still are disproportionately affected. And so, as part of this study, we were really trying to understand why--and my role in this study was to understand the biomarker side of things and if there is something on the biomedical side that could explain this discrepancy or is it a social construct where perhaps if we were to give patients a health worker that could sit with them and say, "These are the questions you should ask," or, "Do you have questions that you didn't understand from your provider?" Just trying to help coach them.

So, a personalized coach is what we like to think of it. And trying to understand if there are changes in the brain that are different, is it possible that African Americans-- we know that they have diabetes and all these other metabolic disorders-- is it possible that they have them longer before they're actually treated for it and that could be the reason why they seem to be impacted. So, these are some of the things that we're curious about and looking into. I don't have the answer yet but it's still ongoing.

[00:13:10] Bouchie: But really important work in terms of improving lives, both for individuals and for families long term.

[00:13:18] Robinson: Yes, definitely. And I guess if there was something that I could say could help is to really just think about your diet and just your lifestyle. Are there things that you can do now that can actually improve your health overall and decrease your likelihood of developing some of these disorders? And there are. We could eat healthier. My lab and I sometimes go out into the community to talk about our research and we like to go to the senior home and I remember going to a senior home and talking about diet and how it impacts the brain and your brain health and how there's little things you can make, you don't have to try one of these fat diets and completely cut out everything that you enjoy. It's okay to have things in moderation but are there small changes that you can make that you can actually sustain? And one thing we talked about was the sugar versus the artificial sweetener. And the seniors hated it. They didn't like the artificial sweeteners. Some of them do have an aftertaste. But if you can just commit to one thing, what's the one thing you can do to just try to improve your diet?

[00:14:28] Bouchie: That's great. As a Southerner, someone who grew up in Alabama and now lives in South Carolina, what does it mean to you to be a researcher working on this health issue in this part of the country? I mean, we know that South Carolina has high prevalence rates of metabolic disorder, we know that the African American community, as we've already discussed, has a higher incidence of these types of health concerns, what does it mean to you to be working on this issue here really in a space where it's so prevalent?

[00:15:10] Robinson: So, there are a couple of things. One is I'm a basic scientist and so as I think about my research, I always want to make sure that it has a translational impact. Something that we can actually bring to the patient to ultimately improve health all around to patients. And South Carolina has the highest levels of diabetes, Alzheimer's disease, stroke, all of these disorders that ultimately I'm interested in. So, this was a great place in the South-- the heart of the Stroke Belt as we know it-- a great place to do my research and really be informed based on the clinical population and make sure that I'm making those same implications in the laboratory to do my studies.

Also, being from the South, my family is impacted. I've had several members of my family that were diabetic, had a stroke, impacted by Alzheimer's disease. So, there's also a personal reason as to why I want to make life better for my children so that this is something-- and ultimately they don't have to take care of me when I get older. So just trying to make lifestyle changes even for myself because I'm from the South, I love the food, I grew up with it. So having to like dial back now as an adult and try to make healthier choices. It's not always easy but it's possible to make small changes.

[00:16:36] Bouchie: And it's worth it.

[00:16:37] Robinson: It's worth it. It definitely is worth it.

[00:16:42] Bouchie: So, we've talked a lot generally about this issue but let's talk about your research and your current research. What is it that you're working on? How are you working to study the impact of diet and obesity on memory function?

[00:16:56] Robinson: Yeah, so again, we use animal models in the laboratory and we try to make it as translationally relevant as possible so we use high-fat diet in our models. And what we're doing is really trying to understand one, if an animal is exposed to a high-fat diet early on in life-- so thinking about how our children like chicken nuggets and hot dogs and french fries growing up-- does that lead to memory impairment? And if we make changes later on in their life, can we ultimately improve or reverse some of those memory impairments? So that's kind of what my research is focused on and trying to understand the mechanism.

So, what is driving it, ultimately? And as I discussed before, one of the things we're looking into is insulin and the impact that insulin has in the brain. So, we're trying to use various drugs that can ultimately increase insulin levels in the brain. So whether it's targeting the actual mechanism to help get insulin across or whether it's a direct approach with using, for example, intranasal insulin that bypasses the blood-brain barrier and it doesn't cause a peripheral drop in glucose levels to deliver it that way, to increase insulin levels in the brain and how does that impact memory and actually how does it impact recovery from injuries such as stroke? So, there is a process of moving basic science work towards the clinic so that we have that bench-to-bedside model that moves it towards patient care.

[00:18:32] Bouchie: You mentioned particular types of things like the intranasal insulin. What does the pathway look like for you as you're looking at your research which is on the bench side for how it could possibly move towards bedside and really be available to patients to help improve their care and their lives?

[00:18:52] Robinson: So that's a really great question and something that I'm always thinking about. And to do this, I collaborate with clinical scientists who actually can do some of the clinical trials. So, I have partnerships ongoing right now and my stroke research was part of the Stroke COBRE here at MUSC which is mainly involved in clinical trials for patients, or mainly sees stroke patients for rehab. It's a rehab facility for stroke. And I partner with some of the scientists there and we are constantly thinking about how we can take the intranasal insulin that we see because we've seen tremendous impact at least on the pre-clinical side in the animals where it improves survival, it improves some of the deficits after stroke, and it also improves recovery in terms of motor and cognitive impairment. So, we're interested in how we can actually bring this to patients and it's something that we're working on and we're working towards, so hopefully we'll get there soon. But one thing about the intranasal insulin is that it's already been in clinical trials. So, there's been trials with intranasal insulin for Alzheimer's disease, for example. And the initial trials were promising but I think the current trials are probably on hold at the moment. So, this is something that is translationally relevant that we can bring to the bedside. There's just a few more steps that we have to overcome.

[00:20:27] Bouchie: Right, right. I want to ask you about mentorship, which is something we've talked about before on the podcast, and I think it's so important and it's clear to me, looking at your lab page, your lab webpage, that you have lots of folks who come in who are hoping to learn not only about the specific issues that you're studying, but also about that process of becoming a basic researcher and how important the basic research is to the whole multitude of discoveries that we can make to improve health. Can you talk a little bit about the importance of mentorship to you and sort of what you're doing in your lab to seed that next generation of researchers?

[00:21:16] Robinson: Yes, mentorship is the most rewarding part of my work that I do and it's something that I hold really near and dear to my heart. It's more about, to me, the transference of the knowledge that I have and trying to impart in my students that same not only just rigor in terms of science but also having that enthusiasm for science and some of the results and being inquisitive and asking questions. So, I love mentoring and I think that good mentorship is important and something that we should all strive for. Because ultimately, it helps to move science forward, bringing individuals together from various walks of life, having a diverse lab group which you probably notice from my webpage, I do all levels from high school all the way through as a post-doc. It's important to have that diverse environment and to get various perspectives in order to move science forward.

[00:22:22] Bouchie: I really want to leave our listeners today with some ideas and some thoughts about what they can do to live healthier as it pertains to brain health. And you already mentioned earlier diet, which of course we all know can be challenging especially when you live somewhere like Charleston, too, where the food is really incredible. But there are also other things that we can do as well that can help decrease our risk for maybe metabolic disorders and therefore decrease our risk for memory loss later. What are some of those things?

[00:22:59] Robinson: Yeah, so in addition to diet, another thing is exercise. Exercise is very important. I struggle with that myself. But if you can just commit to doing just a little bit, like perhaps instead of taking the elevator take the stairs for a flight. But just little things to do. Take a class that's fun and not just having to walk on a treadmill. But think of activities that you enjoy doing and that you can do no matter what your age is. Swimming is a really great way to get exercise. But just thinking of exercises that you can do. Ultimately, that also improves your brain health. Anything that you do to keep your body active and make your body healthier even peripherally ultimately has a positive impact on your brain as well.

[00:23:55] Bouchie: So, we're going to take small steps towards eating better and moving more and we're going to keep researching how those things and other things can help us live longer, live healthier, and keep our brains intact as we age.

[00:24:18] Robinson: Absolutely.

[00:24:19] Bouchie: Great. Well, thanks so much for being with us on Science Never Sleeps.

[00:24:22] Robinson: Thank you. It was a pleasure.

[00:24:25] Bouchie: We've been talking to Dr. Catrina Robinson about her research to understand the connection between metabolic disorders and brain health. You can find out more about the research happening at MUSC by visiting research.musc.edu. Have an idea for a future episode? Send us an email at ScienceNeverSleeps@musc.edu.

Science Never Sleeps is produced by the Office of the Vice President for Research at the Medical University of South Carolina. Special thanks to the Office of Instructional Technology and Faculty Resources for production support on this episode.