(24 mins) In this episode, Harold Reitman, M.D. speaks with Malav S. Trivedi, B.S., M.S., Ph.D.. Dr. Trivedi is an Assistant Professor at Nova Southeastern University, and a researcher in their Center for Collaborative Research (CCR). He discusses what epigenetics are, explores the cellular basis of conditions considered neurodiverse, and elaborates on the important research happening at Nova Southeastern University on the brain through theirTRED (Translational Research and Economic Development) and CCR.
For more about Dr. Trivedi, check out his professor profile at Nova here: https://pharmapps.nova.edu/profile.cfm?BioID=mtrivedi
For more about Nova Southeastern University’s CCR (Center for Collaborative Research), visit: http://www.nova.edu/research/ccr/
For more about Nova Southeastern University’s TRED (Translational Research and Economic Development), visit: http://www.nova.edu/tred/
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HACKIE REITMAN, M.D. (HR): Hackie Reitman, welcome to another episode of exploring different brains and today, right here in our studio, we have a real live neuroscientist from Nova Southeastern University. He does a bunch of research on things I can’t even pronounce but you’re going to hear what a real neuroscientist is doing, exploring different brains, Dr. Malav Trivedi from Nova Southeastern University. Welcome.
MALAV TRIVEDI (MT): Thank you, sir. Thank you for having me.
HR: Thank you for being here. Now look, I want to get right to the quick. I want to know about these things I can’t pronounce like epigenetic base gene expressions and things like that. Tell me what is it you do over there.
MT: Let’s get right into it. Epigenetics is a phenomenon, which happens on top of your DNA. So people say like, you know, your genetics is altered, your genes are changing, and your DNA is changing. Well, what really changes is what controls that DNA. So if there are environmental factors that control your DNA, that can control how the DNA is being silenced or the how DNA is being expressed. We start with a single cell. Every single living human being starts with a single cell and that single cell develops into a brain cell, that single cell develops into a kidney cells, that single cell develops into a liver cell, but all those cells have the same DNA component.
HR: Okay, now let me stop you there. So DNA, you’re watching quickly, they control everything, they’re your heritage, they’re your genes and everything.
HR: So you’re talking about?
MT: Something that controls that.
HR: And we call that?
HR: Malav Trivedi is telling you, the thing that controls the DNA, that’s controlling everything. So you are right to the top in a way.
MT: Right. Exactly at the top of what controls the DNA and so if you think of DNA as a string, the things that make the string being expressed or silenced in one cell versus the other because your neuronal cell doesn’t need the same stuff or cargo as your liver cell or your kidney cell because they function differently. Your brain cells make memories. Your kidney cells filter things. So they differ from each other and that is controlled by what controls the DNA or by epigenetic changes and that’s what we study in our lab, especially in the brain as to how the environmental factors like stress, like diet, like nutrition, like exercise or the chemicals. The quad pollutants. How’d that affect the epigenetic changes and that makes one neuron susceptible to all these stressors or environmental components.
HR: You don’t have to be a rocket scientist to know that exercise, diet, cutting down on your stress. It’s not only good for your whole body, good for your health, it’s good for your brain and now we’re hearing from Dr. Malav Trivedi at Nova Southeastern University, why that is because of what’s controlling the very DNA that runs all of your different kinds of cells. Keep going. I’ll be your interpreter.
MT: Thank you.
HR: Cause I don’t know if our audience is as smart as you or as dumb as me so I’ll kind of interpret it a little.
MT: So the string of DNA is bound to proteins. Think of them as spools for your DNA. Those are called as histones and so those spools control whether the DNA is unbound or the DNA is tightly bound and based on whether a DNA is tightly bound on the spools or loosely bound, that can affect the gene expression. So those decorating marks like methyl groups, ch3, methyl groups on the DNA, control whether the DNA is loosely bound or tightly bound and that affect the gene expression and that can affect whether it will be a neuronal cell or whether it would be a kidney cell.
HR: It has to do with how tightly wound up and bound they are.
MT: Yes. Exactly and so those marks, those decorating marks on the DNA, the methyl groups are affected by environmental pollutants, are affected by stress, are affected by pesticides, insecticides, organic compounds and they can also be regulated by a proper diet, proper nutrition, proper metabolism and exercise. So what we study in the lab is in different neurodevelopmental diseases or neurodegenerative diseases, how these marks are affected. First, so we can do a diagnostic purpose and then, what can we do to intervene into these marks for a therapeutic approach or for a treatment approach.
HR: Now, Dr. Malav Trivedi is in Nova Southeastern University and he just mentioned, we’re going to throw a couple of initials at ya’. One of them he just mentioned, he’s going to explain to it what it is in a minute, is over there at Nova Southeastern. The CCR and then, maybe later on, we’ll talk about tread. Explain to our audience the concept of CCR and what it really is.
MT: With the blessings of the board of member of Nova Southeastern University, we have had a state of art center for collaborative research which stands for CCR. It is an 80 million dollar, 125 thousand square feet of research space available for researchers to conduct a state of a research with all the innovative tools and technologies. You apply them to basic science, to applied science and we also have an in-house clinic where we can start seeing patients and conduct human clinical studies to try and understand the disease path of biology as well as start treatment approaches and treatment therapeutic purposes. So CCR stands for Center for Collaborative Research, where we have researchers from all across DC spectrum. So we have people who study neuro-immune diseases, people who study chronic fatigue syndrome, people who study autism, people who study on Alzheimer’s, cancer and we also have people who are studying stem cell research to try and come up with therapeutic approaches using stem cells for neural regeneration or for immunotherapy purposes in the center. So we have people from all different spectrums of science, from different diseases and trying to understand and trying to treat those diseases.
HR: In the Center for Collaborative Research, that is also hooked up globally with center?
MT: Yes. It’s good that you mentioned that. So, in the Center for Collaborative Research, we have about 5 or 6 different faculty members from Karolinska Institute, which is in Sweden, Stockholm and that is the place where the Nobel Prize is given or the committee is come from that Institute and we have been really lucky to have some of those faculty members from Karolinska Institute to set up their shop or to set up their labs at the CCR, where they collaborate with us. The researchers who are based here and we have faculty exchange programs, we have student exchange programs and research exchanges where we collaborate with them, they collaborate with us over here. So we have knowledge base globally not just localized to Fort Lauderdale.
HR: This is a nice segway to introduce, what is the relationship between the CCR, the Center for Collaborative Research, our mutual friend, the great doctor, Tom Temple and TRED, Translational Research and Economic Development there? How do they all connect?
MT: So, this was Dr. Tom Temple and president Hamberry’s vision for bringing together not just basic researchers or basic scientists who study cells or who study organelles in the cell but to apply those kind of things, transnationally, to try and treat diseases. So what I mean by that is, what I do in the lab on a day-to-day basis, how does that affect or how does that cure a disease in a patient tomorrow or day after tomorrow and that’s the vision which Dr. Tom Temple brought into Noah Southeastern University when he joined as a VP of research and he formed this institute called a straight or translational research and economic development to translate the research that we do in the lab into therapies for tomorrow for different diseases and the place where this research is being conducted is at the CCR. So CCR is the hub of the research for NSU and TRED is the machine that translates that research into therapies for tomorrow.
HR: On a larger sense, the visionaries at Nova Southeastern University, George Hamberry, the president and the senior vice president, Dr. Tom Temple was a very illustrious history with the University of Miami and like myself, is an orthopedic surgeon by birth but certainly their vision is being fulfilled there and now we see what’s been missing through an up till recent times is that link between the research translating it into getting something done so that it goes from the concept to the reality to the marketplace.
MT: It is exactly the bench site to the bedside concept like you know what I do on the lab bench, it translates into bedside therapies for patients. So that’s what the vision that Dr. Temple is fulfilling right now at NSU.
HR: How do you get into this?
MT: It’s a long story but I’m a pharmacist by training and I did not want to be just a mediator or are a manager of diseases like you know at the bedside like you know just giving the medication or dispensing medication, so I really wanted to understand the petal pathology of the diseases and understanding what happens at the right the trigger of the disease or what causes that disease and that’s what led me to understand and take masters for pharmacology or pharmacircular sciences after finishing my pharmacy degree so I went to into masters and then I did a doctoral degree as well in pharmacology trying to understand the mechanism behind diseases rather than just directly dispensing drugs. So I went during my doctoral thesis, I got to understand the neurodevelopmental diseases like autism and the pathology of autism and that’s what really fascinated me to undertake my research going forward. Especially while I was doing my doctoral research, I found out that the rates of autism are skyrocketing. When I started my PhD, the rates of autism we’re about one and 120. So every one kid in 120 kids were getting diagnosed with autism spectrum disorder. By the time I completed my doctoral research, the rates were about 1 in 44. Which was a span of four or five years and so I took it upon myself to try and understand as to what explains this or why is it that in five or six years, the rates have gone so higher and that’s what I’m pursuing going forward as in terms of understanding the neurological basis for neurodevelopmental as well as neurodegenerative diseases like Alzheimer’s.
HR: What year were you born?
HR: Okay, so in 1985, talking about how things have changed. Along with the autism rate, not just autism, it’s anything you want to keep track of with brain wiring, PTSD, depression, anxiety, stress, Alzheimer’s was a certainly skyrocketing. I mean from autism to Alzheimer’s and everything in between. What’s changing? Is it the DNA? Is it the epigenetic? Is it the food stimuli? Is it the environment? Is it the exercise? Is it all of the above? So why don’t you comment on putting it in the context of the changes you’ve seen in neurodiversity, not just autism too, and how you see the whole big picture from your unique scientific point of view.
MT: It’s really interesting that you mentioned that, if you think about it, the role of diet and the portion sizes of diet, as well as nutrition, along with the environmental factors, all of the above have changed from 1985 to 2015 or 2017. Now, if you think about it from a scientific perspective, the more the bad thing increases at the same time to maintain the status quo, you need to increase the good things as well. So what I mean by that is the more the environmental pollutants, the more the insecticides, the more the pesticides, the life stress increases at the same time we have to maintain our nutrition, we have to maintain our diet, we have to maintain our exercises, which is not happen and so what’s going on is the fire is going up and the level of fire extinguisher is going down. What I mean by that is, if you think about in-metabolic perspectives, our need of a demand for the energy is going high but we have really less and less and less capacity to combat with that energy demands, high energy demands. In terms of scientific perspectives, what I mean by that energy demand is in terms of antioxidants. When you are stressed, when you are exposed to insecticides or pesticides or environmental pollutants, you generate oxidative stress in your body. What I mean by oxidative stress is high levels of reactive oxygen species or chemical toxicants in your body. To combat that fire, you need high levels of antioxidants like your blueberries, red berries or vitamin C. One of the most or maybe the most important antioxidant in your body is something called as glutathione, GSH, and the levels of that GSH in your brains are the least of the whole body. So here you have high levels of oxidative stress in your brain and you have the least quantity of antioxidant in your brain to combat that, so any minor changes in that antioxidant level directly affects the activity of your brain, directly affects the neuronal firing and the wiring in your brain, making it more prone or more vulnerable to effects or the neurodiverse effects from a normal development.
HR: What a great explanation and if we think of it, the brain weighs about 10 pounds or something. Whatever it is.
MT: Two pounds.
HR: Two Pounds, not 10. Two pounds uses up what percentage of energy in the whole body.
HR: 20%. See a little 2-pound brain you got up here is using up 20% of the whole energy. We are in an energy crisis as you just heard from Dr. Malav Trivedi of Nova Southeastern University and so we have got to use good fuel and then metabolize that fuel with good exercise and then affect all the, to use a highly scientific term, “stuff” he’s talking about that controls our DNA and everything else so we can live happily ever after.
MT: It is a lot about healthy aging and healthy living as compared to being prone to diseases or prone to you know the effects of the chemical environmental effects. So and that’s what we study in the lab right now on how those chemical toxicants or chemicals environmental factors can impinge on your brain and lead to all neurodevelopmental trajectory, if we intervene at initial stages as early as possible, ASAP, then you can try and negate or at least lessen effects that those compounds or leaders position will have.
HR: And just for the purposes of this interview, let’s specify some of the other neurodiverse entities you’re speaking about that it’s the same basic deal with. Let’s just name some for audience.
MT: So I just talked about the healthy aging and so it’s really interesting that at different stages of your life, if you have altered anti-oxidant or all the epigenetic changes, we have and others have also shown this that it can contribute towards different neurological diseases or neurodiverse phenotype. So if it’s early on, there is something neurodevelopmental or neurodiverse patterns like autism, ADHD, Asperger’s, if it’s eighteen to twenty five or eighteen to thirty that can contribute towards schizophrenia, then if you are lucky enough and if you skip that, then you would starting forty to sixty is when you have genetically discussion towards Alzheimer’s, Parkinson’s and then 60 to 80 is neurodegenerative disease like Alzheimer’s and Parkinson’s diseases so across the lifespan depending on how vulnerable based on your genetics, based on your environment, how vulnerable you are to having neurodiverse patterns can contribute towards different neurological manifestations. So starting right at neurodevelopmental all the way towards neo degenerative and so we study in our lab at the CCR, we study early on autism spectrum disorder and we find that in kids with autism and ADHD, they have accelerated aging same as what people will have at sixty or eighty years of age and so they have skewed the developmental secretary right then and there. Which is really, really interesting because if you think about them, if you think about their mind or their brains, they are still learning the language, they are still learning the social skills, they are still learning the vocabulary and they are already, like you know, their brains already like here at the sixty to eighty years of age. so they have accelerated aging right then and there, especially their brain.
HR: And that’s why we at different brains are trying to get everybody under one roof and to push that concept. It’s about all of these entities and all of our brains but you bring up an interesting point. The silos they are all in now by entity are actually, if you’re going to have silos which we shouldn’t have, but if we’re going to have them, they should be lumped by age. It shouldn’t be the intellectual disabilities here and the neurological here and the mental health psychiatric here. No. They’re all depends how old you are and what your epigenetic background is.
MT; All your metabolism in the brain is and so it’s metabolic and epigenetic combined together because what we have found in the lab is that metabolic phenotype also controls your epigenetics so that antioxidant levels can directly control your epigenetics status as well and so yes, you bring up a really good point about like you know, not putting people in the silos based on just a mental health or intellectual disability but putting them in terms of their physiological phenotype as to what’s going on inside their brains and understanding the physiological manifestations so that you can treat them. Just because a medication is available for schizophrenia or Parkinson’s doesn’t mean that it might not be applicable to kids with autism. If you start understanding the physiology of it, then you might be able to treat them with different combination and permutations of not only drugs but also nutrition.
HR: Dr. Malav Trivedi, it’s been a pleasure having you with us today on exploring different brains and we look forward to having you back because we haven’t quite finished our conversations. Thank you so much for everything you’re doing.
MT: Thank you for having me. I’ll be happy to be back.
This video is owned by Different Brains Inc, kindly donated by it’s original producer PCE Media LLC.