Understanding Alzheimer’s and Parkinson’s at the Cellular Level, with Dr. Malav Trivedi of Nova Southeastern Univ. | EDB 93
(25 mins) In this episode, Harold Reitman, M.D. continues his conversation 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 the importance of nutrition for the neurodiverse, what happens in the brains of people with Alzheimer’s and Parkinson’s disease, and the impact of brain trauma. For part one of his interview, click here.
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): Hi I’m Dr. Hackie Reitman welcome to another episode of exploring different brains. We’re glad to have back for another visit our continuation with Dr. Malav Trivedi a nueroscientist of Nova Southeastern University. Malav, welcome!
MALAV TRIVEDI (MT): Happy to be back again.
HR: Well I’m looking forward to maybe you and I collaborating because what I’m–I’m approaching this almost as a layperson even though I have an MD. But the part of the translation addition to translational research and economic development is to translate the brilliant discoveries that you’re making into what Joe-Average-Person can really understand and incorporate into their lifestyle because it’s one thing to start eating blueberries if you think it’ll be really good for you because it’s going to do this and that as opposed to you know the way your DNA strands wrapped up too tight.
MT: No, it’s good that you mentioned that because what we are doing at the Center for Collaborative Research is we are trying to integrate brain research and integrated nutrition. So we are trying to bring up how nutrition–just normal, your blueberries and your red berries, along with some vitamins or multivitamins–can promote your brain functioning, your brain wiring and brain firing. And that’s what we want to study at the so-called “Brain Center”. B-R-A-I-N, which stands for brain research and integrated nutrition. So B-R-A-I-N.
HR: And it’s interesting you separated the nutrition from the exercise. I’m not saying that critically I’m saying it’s interesting.
MT: No, it is interesting because exercise–what we have found is that nutrition is the key promoter. Exercise adds on by itself. None of the players play as much important role as nutritionist.
HR: So to those of you fast food people out there, you just want to keep eating fried junk and processed food and then go to LA Fitness and workout to your heart’s delight, it’s not going to do for your brain what a good diet itself would do in addition to exercise. So while nutrition can be a standalone exercise only works well with proper nutrition.
MT: Yes and the old saying “you are what you eat” really applies to your brain for sure.
HR: From your point of view, what are the biggest challenges facing us regarding neurodiversity?
MT: Some of the biggest challenges that faces the neurodiverse community is understanding that one phenotype of a disease or of one phenotype of a neurodiverse person does not put them in silos or put them into a box and understanding that the same physiological or pathological changes can occur in different diseases as well. So understanding how there are underlying changes in the physiology from different diseases rather than just putting them into box from a autism spectrum disorder versus ADHD versus Asperger’s versus Alzheimer’s. Saying they all are different diseases. If we try and understand what are the underlying physiological changes occurring or underlying pathological changes occurring if we try and identify them, we might be able to treat them better. we might be able to understand them better diagnose them better and ultimately lead to better treatment purposes rather than tackling them individually. so that’s what like you know understanding the neurodiverse, accepting it and then understanding why and how they are neurodiverse is what I think is the challenging part right now in terms of scientific and research undertakings.
HR: Now one of the things I say about Different Brains sometimes is we’re covering everything from autism to Alzheimer’s. Okay? And everything in between. These are two very common things, two common entities that are increasing at very high rates. And while there may be some argument, which I don’t go for about autism just being diagnosed more. I know that it’s increased in frequency. Alzheimer’s there can be no doubt that that is increasing big-time. And I feel that all neurodiversity is many, many, because of some reasons of Darwinian nature and so we’re talking about these getting the things out of the different silos. Which by the way is how our grant system is set up yet. And we’re trying to get into now is the whole continuum. And let’s talk about autism and Alzheimer’s. Let’s talk about Alzheimer’s which is increasing at an alarming rate.
MT: No, you’re absolutely right about in 2020 to estimate there’s going to be several million people in the US that are going to be diagnosed with or suffering from Alzheimer’s. And so we have taken Alzheimer’s into account in our lab right now. And what we study is something called as vitamin B12. And what we find is that patients with Alzheimer’s disease especially in their in their brain, they have lower levels of vitamin B12. And so what we are trying to study right now is if we can diagnose the same vitamin B12 levels in the periphery–what I mean by that is in the blood cell–and try and see if that correlates with their brain vitamin B12. And if we can treat Alzheimer’s patients with something that delivers vitamin B12 to that brain, the way we are doing that is by developing intranasal approaches to deliver vitamin B12 through nose to the brain. And so what we are trying to do is use nutrition, something which comes out of nutrition vitamin B12, is comes out of diet. And so what we are trying to do is, something that comes out of nutrition, like vitamins, can be used to treat diseases like Alzheimer’s. And so what we are studying right now is how vitamin B12 can help people with Alzheimer’s diseases. So first we identify vitamin B12 levels in their plasma or in their blood. try to coat it with their assignment symptoms or dementia, and try and see if early on we get them started on vitamin B12 treatments. Vitamin B12 injections are of course helpful but vitamin B12 passes really low through the blood-brain barrier into the brain. so what’s also interesting is we and others have showed that the transporter, or the carrier that transports vitamin B12 inside is also responsible for transporting a protein which is known to be elevated in Alzheimer’s disease outside of the brain. So something that transports vitamin B12 inside is responsible for transporting something that is harmful for Alzheimer’s outside of the brain. But in people with Alzheimer’s disease, that protein called megalin, or lRP2, is deficient. So it does not transport vitamin B12 inside the brain and does not transport the harmful amino peptides which are elevated in Alzheimer’s outside of the brain. And so what we are trying to do is we are trying to see if intranasal delivery can help people with Alzheimer’s diseases, especially and dementia.
HR: And this is a segue into–especially with your pharmacy background into multiple vitamins and pharmaceutical preparations for various nutrients and vitamins and everything. There’s so much we see in the media, supplements or not, don’t have to be FDA proven or approved or anything. And you can pretty much say about any supplement what you want. And we all know that generally speaking, you’re much better off getting your nutrients from the natural food than any pharmaceutical preparation. Tell us from you–you’ve an excellent background not only is a neuroscientist but with your pharmacy and everything else. Give us the holistic picture if you will of multiple vitamins and vitamin supplements.
MT: So multiple vitamins and multiple vitamin supplements are definitely helpful but you have to be really cautious as to how much you are using it when you are using it. And it’s not that one key applies to all locks. So depending on why you are taking it, who you are, how much dose you need. So the dose, the timing, the duration of the treatments and do you really need it? How low you are because you might be taking a multivitamin but your vitamin B12 levels are already normal. So you don’t need that multivitamin tablet, you just need a couple of other vitamins that are not normal range in your body so identifying with the help of a doctor or with the help of diagnostic tests as to what levels are low and then going about a multivitamin approach will be much better as compared to just popping a pill and good about yourself saying, “I took my multivitamin, so I’m good.”
HR: We were talking about vitamins and the bottom line is, is it kind of depends in the way. Now do you do testing for vitamins levels?
MT: As of now, yes, but we are not yet clear certified so we cannot do clinical assessments but there are lives out there and I can I can be contacted for reaching out by other patients if they need to but there are labs out there that will measure your vitamins. Like vitamin Diagnostics is one of the one of the labs who can measure our different vitamin levels, who can measure those antioxidant levels that I mentioned about the glutathione levels, as well as some of the amino acids that support the glutathione synthesis. They can measure all of them for you and they can give you a full report based on your own blood profile. And then you can take that to a doctor or a nutritionist or a registered dietitian and consult with them for your specific vitamins.
HR: And you’ve introduced another variable that this little 2-pound organ you’re carrying around in your skull that uses 20% energy, that not all of the nutrients and vitamins can get through that blood-brain barrier. And even if they can, the transport mechanism might be a little suspect–
MT: In diseases, yes. And in any other basis, especially in disease patients. So like Alzheimer’s diseases is one of the hallmarks of the deficient transporter activity.
HR: Alright so now in your logic based on everything you’ve told us so far and talking about different neurological, mental, intellectual, developmental, differences across the age spectrum, tell me this. Why does such a large proportion of Down syndrome patients develop Alzheimer’s disease? I believe it’s like forty five percent or something like that.
MT: One of the key features that other people have studied for Down syndrome is the oxidative stress and the levels of antioxidants. And they have reported low levels of antioxidants in post-mortem brain samples with kids with Down syndrome. So what that means is if they do survive enough, long enough, then their brains are already decreased antioxidant capacity, increased oxidative stress. That means if they do survive long enough for sixty or seventy years of age, their brains are more vulnerable to insults, more vulnerable to oxidative stress, as compared to other normal aging population. That’s the reason that they are more prone to developing Alzheimer’s, which is basically neurodegeneration, which basically is cell death often by the brain cells or the neurons. And so because they have that elevated or predisposed towards elevated levels of oxidative stress, that can promote cell death. That’s the reason that they can develop higher levels of Alzheimer’s in especially in people with Down syndrome.
HR: Tell us your thought processes based on your research and everything you know relative to Parkinson’s.
MT: So Parkinsonism, again, is a similar phenotype at least metabolically. One of the key hallmark features of people with Parkinson’s disease is dopaminergic cell loss. What that means is the brain cells that make dopamine a neurotransmitter are dying in people with Parkinson’s disease. And metabolically or physiologically, those neurons or the brain regions where those neurons are located, have elevated levels of oxidative stress. And that promotes the cell death. And so that brings back to my point of identifying and underline metabolic feature for Down syndrome, for autism, for Alzheimer’s, for Parkinson’s, that is that oxidative stress. Again you can say that there is a chicken or the egg story, which came first? Whether there was oxidative stress first or whether there was cell debt and that promoted the oxygen stress. But the key feature is that there is oxidative stress. Now if we start treating that, we might be able to intervene or at least slow down the symptoms of Parkinson’s, slow down to the symptom of Alzheimer’s. We are not trying to treat them, we are just trying to make them prolong.
HR: Talk to us about some of the imaging techniques that are used.
MT: So some of the imaging techniques that currently people use are MRI–the magnetic resonance imaging–that I talked about. Another one is called BOLD imaging–blood oxygen level dependent imaging. Something else which recently has come into play is MRS. Which is magnetic resonance spectroscopy. And what that measures is it uses a fenton metabolite. Say you can use antioxidants, like glutathione, or you can measure lactate levels which is another metabolite in your body. And you can measure those things in a live animal or patients in the brain so we don’t need to take out the brain anymore to measure things. we can do it inside the brain in an intact brain in patients with these advanced imaging techniques like MRI and NMRS so we can measure antioxidant changes in the brain early on and we can diagnose them and we can see and compared to controls are their levels low or are the levels high? And what can we do about them? So at early on we can start diagnosing whether these participants or these patients or these people have low levels of antioxidants or are they more prone to oxidative stress? And what are going to be the long-term consequences with that?
HR: I think I know the answer to this based on what I’ve learned from you today. But I want you to explain. Take us through what’s happening to one’s brain if tonight say I have a stroke.
MT: If you–God forbid it, but if you had happened to have a stroke tonight, basically what would happen is there the neurons will stop receiving the blood that they were supposed to receive say in a specific region. And that is going to stop the flow of oxygen to those neurons. And that is going to, in turn–it’s going to create a chain of sequence reactions that is going to make that neuron first go through a panic stage trying to compensate for the loss of oxygen, trying to compensate for the loss of blood. And then eventually it’s going to lead to neurodegeneration. Saying “I do not have enough resources, I’ll have to kill myself.” The cell, “this is what I’m going to happen.” so the neurons will end up dying. So it’s dependent on in a time-dependent manner. So starting from stroke all the way towards neurodegeneration, it’s a long process but that is what’s going to happen eventually.
HR: One of our Exploring Different Brains interviews was with our friend Derek MacFabe up in in Canada, who is one of the gut-brain pioneers as you know, who explained to me–if I was understanding correctly–that the gut has more neurons than the brain. And talk to us about the neurons in the gut and the gut-brain relationship.
MT: So it’s interesting that you mentioned that it brings me back to that the whole “you are what you eat” kind of a process and then that links. The gut-brain access is really an upcoming field especially because people have started finding that there are more neurons as he mentioned in the gut than there are in the brain. But they are called as the enteric neurons which are located in the in the gut. And so the microbial community inside the gut can metabolize your diet, can affect your diet, and can secrete chemicals or chemical messengers that can affect the neuronal population as well as it can pass through your blood-brain barrier and it can affect the neurons in the brain as well. So it does not just affect the neurons in the gut, it can also affect the neurons in the brain. And so the microbiome, the gut, the enteric gut neurons, as well as the neurons in the brain, they are directly correlated and that is why it brings back to that simple notion that you are what you eat
and that’s why the nutrition can affect your brain.
HR: Dr. Trivedi, what we’re into here at Different Brains and what we’re into like when I wrote the Aspertools book is giving real tools that people can use in real knowledge that can be helpful to them. A lot of it is kind of controversial where it probably shouldn’t be. We try to get everybody to get along why can’t we all just get along and everything? Can you speak a bit about the genetics regarding predictability and things of this nature say what you know some of these entities?
MT: Yeah, so it’s interesting that you mentioned that. So what we study in the lab is GxE–which is G stands for genetics, X which means combined with, and E. so G, genetics, and E for environment. So what we study is how genetic predisposition plays a role along with the environmental factors to manifest into neurodiverse phenotype. Now what we study in the lab is the X, which stands for your oxidative stress or stands for your metabolic phenotype. So your genetic predisposition, your metabolic phenotype, and your environment, how they all three come together for neurological manifestations. And so the genetic theory of autism has been controversial, but what we study is not one versus the other. What we study is how they both are combined together and manifest itself in in a neurodiverse phenotype
HR: And this is what we’ve been maintaining at Different Brains, as with everything on earth that I know of. Everything is multifactorial. And what we’re doing here and what you’re doing at Nova Southeastern University is giving real tools. For instance, no matter what your genes, what your brain is, no matter of anything, a good healthy diet, a good exercise program, a decreasing of your stress, and something we really haven’t discussed today that’s very important, which probably involves all of those things is socialization, is also very, very important. And no matter what your genotype and phenotype and everything else, these things are important. so we have to consider our overall environment, and everything about us.
HR: Now if someone wants to know more about what you’re doing, how do they find out?
MT: So I do have a faculty profile at Nova Southeastern University but I’m more than happy to connect with them my information. You have my information and you can always direct them towards me. And I’m located at the CCR so I’ll be happy to show them the research facilities that we have as well as, like you know, showcase some of the research that we do at the CCR at NSU. So I’m more than happy to connect with them and guide them in whatever questions they have.
HR: What are your career goals? As if you’re not doing enough already.
MT: Absolutely. I am. I would be happy if we can understand the manifestations that we have created ourselves in the environment and how that is feeding back into our own physiology. So that’s what I want to understand we take we talk on every day that there’s climate change, there’s climate change, there’s like–you know we are inducing climate change. We have to stop ourselves and think how that is affecting back us. How is that affecting not just in terms of environment but how is that affecting our physiology? How is that affecting our brain function? And so if I am able to understand during my career on what role does it play, I’ll be a happy person
HR: We’ve been speaking here today at Exploring Different Brains with Dr. Malav Trivedi of Nova Southeastern University. Malav, it’s been a pleasure to have you here again. thank you very much for being with us.
MT: Thank you so much for having me
This video is owned by Different Brains Inc, kindly donated by it’s original producer PCE Media LLC.
Different Brains® Inc. founder Harold “Hackie” Reitman, M.D. is an author, filmmaker, retired orthopedic surgeon, former professional heavyweight boxer, the past chairman and president (and current board member) of The Boys and Girls Clubs of Broward County, and a neurodiversity advocate. However, it was his role as a father that led to the creation of the DifferentBrains.org website.
Hackie’s daughter Rebecca grew up with epilepsy, 23 vascular brains tumors, and underwent 2 brain surgeries before the age of 5. Her struggles and recovery put him on the road to, through 26 professional heavyweight boxing matches, raising money for children’s charities (to which he donated every fight purse).
Rebecca eventually went on to graduate from Georgia Tech with a degree in Discrete Mathematics, and Dr. Reitman wrote and produced a film based on her experiences there (The Square Root of 2, starring Darby Stanchfield of ABC’s Scandal). After graduation, Rebecca received a diagnosis of Asperger’s syndrome. Hackie, shocked at his own ignorance of the topic despite being an M.D., embarked on years of research that culminated with his book Aspertools: The Practical Guide for Understanding and Embracing Asperger’s, Autism Spectrum Disorders, and Neurodiversity (released by HCI books, publishers of the Chicken Soup for the Soul series).
This experience revealed to Hackie the interconnectedness of the conditions that fall under the neurodiversity umbrella, while alerting him to the in-fighting and fractured relations that often plague the organizations tasked with serving the community. Convinced that overcoming these schisms could help all of society, Hackie forged the Different Brains philosophy of inclusive advocacy: “Supporting Neurodiversity – From Autism to Alzheimer’s and All Brains In Between”.
In the company’s initial years of operation, Hackie self-financed all of the content on DifferentBrains.org, all of which offered free to view to the public. Currently he is the host of our weekly interview show Exploring Different Brains, writes blogs for the site, and tours the country speaking at conferences, conventions and private functions, all with the goal of improving the lives of neurodiverse individuals and their families, and maximizing the potential of those with different brains. Separate from Different Brains, Hackie is the founder and CEO of PCE Media, a media production company focusing on reality based content. He recently co-executive produced the documentary “Foreman”, the definitive feature documentary on legendary boxer and pitchman George Foreman.