The Other CTE: Toxicants & Your Brain, with Marcia Ratner, Ph.D. | EDB 207


World-leading neurotoxicologist and research scientist Dr. Marcia Ratner discusses Chronic Toxic Encephalopathy

(24 minutes) Marcia’s research focus is neurotoxicants, chemicals that can cause brain damage. Marcia is also a project manager for the Department of Pharmacology & Experimental Therapeutics at Boston University, and she also provides neurotoxicology-related consulting services resulting in major court decisions and policy change involving neurotoxicants. Join Hackie and Marcia as they look at a lesser known form of CTE: Chronic Toxic Encephalopathy.

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Welcoming back Dr. Marcia Ratner

DR. HACKIE REITMAN (HR): Hi, I’m Dr. Hackie Reitman. Welcome to another episode of “Exploring Different Brains”. And today I’m very excited to have with us all the way from Boston University School of Medicine, my alma mater, the wonderful Dr. Marcia Ratner the neurotoxicologist and so much more. Welcome Marcia!

DR. MARCIA RATNER (MR): Hi Hackie. How are you? I’m glad to be back with you again.

HR: Well thank you so much for coming. Why don’t you do a proper introduction of yourself, because you got so much going on it’s hard for me. The way my brain is wired to get it all out.

MR: I’m Dr. Marcia Ratner. I’m at Boston University School of Medicine where I do research looking at the effects of neurotoxicants, chemicals found in the environment and workplace on the brain. I’m interested in how these affect our risk for neurodegenerative diseases as well as how these make us sick all by themselves when exposures are very high, and people get sick from the exposure itself.

The Other CTE

HR: You’re going to talk about the other CTE. What do you mean, because CTE is getting so much publicity now with football and boxing and sports and you’re going to talk about the other CTE? Enlighten us on that.

MR: Right, so that’s exactly it Hackie. So, everybody’s hearing about CTE now in the news with the football players and of course the Hernandez story, you know right near a Patriot player, so people have come to be aware of chronic chromatic encephalopathy which occurs when someone get hits repeatedly in the head as a football player would do and, but there’s another acronym for CTE which is chronic toxic encephalopathy and we can think of toxins chemicals almost like little football players that come along and beat up our brains. And I’m very interested in how those hits to the head, those chemical hits to the head, influence our risk for injury, direct injury to the brain and how those interact with our risk for age related neurodegenerative diseases such as Alzheimer’s.

HR: Fascinating and you know, Alzheimer’s, we really haven’t made much progress on that all these years, have we?

MR: No. In fact, I was recently interviewed about the prospects of some of the drugs that are in the pipelines for treating Alzheimer’s that are going in to sort of clean up the plaques that bioaccumulate in Alzheimer’s. You know BioGen, and other companies, Roche, they have something in the pipeline right now which we’re optimistic that this is really opening the gate to starting to make some progress, but we still don’t have a cure. We have some ideas about what’s involved but we don’t have a cure. But what we’re learning is that other factors can cause similar pathology’s, so with CTE the chronic traumatic type, we see a bio accumulation of a protein called Tau which we also see with Alzheimer’s disease, and so we’re starting to understand that injuries to the brain lead to bioaccumulation of these misfolded aggregated proteins that play a role in disrupting neurological function, ultimately in neurodegenerative diseases.

Fighting Alzheimer’s

HR: Well, I’m going to have to introduce you some time to my good friend Ken Dychtwald of Age Wave, and he’s of the opinion that we’ve kind of scientifically been barking up the wrong tree all these years and he’s trying to stimulate real out-of-the-box kind of thinking in the sense that we’re always starting in reverse with Alzheimer’s and dementia, with the Tau proteins, and the plaques, and the deposits instead of perhaps at the front end. This isn’t Ken Dychtwald talking this is just me, but I really enjoy it when people are trying to look at something entirely differently and I think one of the problems we have is the way the grand system is setup is that you have to show pre-existing work in the field and when someone is bright as you are, when you come up with a whole new way of looking at it, it probably throws you a curveball.

MR: Well, fortunately I’m working on a project now where we’re looking at neural network activity in the brains of an animal model of Alzheimers, which we think precedes the progression and contributes to the progression of the disease so I tend to agree with what you’re saying, I think that when you look at, because I’m a toxicologist and if I look at what neurotoxins can do to the nervous system, I see aggregation of proteins there too and hexane, acrylamide we talked about in my last interview, these cause aggregation of neurofilaments within the axons of nerves and so we know that disrupting axonal transport, disrupting cellular energy functions, mitochondrial functions, ultimately leads to an inhibition of transport of proteins and things throughout the cell and if these things start to mis fold because of aggregates that are bound to them like a covalently bound chemical, they start to mis fold and now they start to aggregate. So this is as you say a biological marker of effect, downstream effect, but it’s not cause all intoxicants we know that it’s the toxicants that’s causing it, and the aggregated protein is merely the re-out that we see so I’m not far from your camp. I have to say that I think that cleaning up aggregated proteins is kind of like mopping up the floor and leaving the sink overflowing without turning the water off.

HR: That was very, very well said, very well said. Talk to us about the difference between the neurotoxicants effect on children vs adults.

Neurotoxicants in children vs adults

MR: Right, so when you know we talked last time about what’s going on in Flint, and I told you that we don’t know yet. Right, so when children are developing, and this is a big difference between children and adults when children are developing they are acquiring language skills, they’re acquiring math skills, and if they’re nervous system is not functioning properly then they’re going to have problems acquiring those skills and that over time, we all know math is accumulative thing. If you didn’t learn basic addition, you’re going to struggle when you get into algebra and never even make it to calculus. It’s really crucial that during this developmental time that when students are acquiring these skills, language and mathematic skills that they’re not having problems because these problems are insidious, and gradually over time, after several years by the time the student enter say junior high or middle school, students who were exposed to chemicals when they were younger, maybe as an infant by the time they get into middle school we really start to see problems with math and maybe English and these problems can interfere with their career prospects and they can get held back a grade. The ramifications are very, very big in children exposed to chemicals because they have long-term consequences on the population at large and on the individual.

HR: And then when you can what you just said, and you look at what happened in Flint, Michigan, and all those kids drinking that water. Talk to us about that.

MR: Yeah, so we mentioned that and as I said last time we don’t yet. So, there is funding to monitor these kids and some of their parents are already starting to report problems. So, I know I monitored the news on this and I know that there are some pending lawsuits from parents who are already noticing behavioral and academic problems in some of their children, but we don’t have the results of a study yet. So, this I sort of anecdotal observations of parents, but we don’t have the results of a formal study yet, looking at the progress of the exposed children vs children who lived in nearby towns similar sociodemographic that wasn’t exposed. That’s the kind of information we’re really going to need to understand the full impact of what happened in Flint.

What to do after exposure

HR: What should a person do? What should a person do if they feel their child has been exposed to neurotoxicants?

MR: You know, the first thing you need to do is, you know, determine if you have a suspicion, but if you, the first thing you should do is confirm that, right, so you can take the child to a local hospital or to their pediatrician and get their blood levels measured for metals. For example, lead, it can be measured in the blood. First thing you should do is document that exposure. Very important to document the exposure because that information is going to become relevant later on. Right, then immediately remove the child from the source of exposure so that you have cessation of exposure, you have to stop the ongoing exposure, and provided that the child is not that sick, then their blood levels should be monitored until they return toward base line. If their elevated very high then chelation may even be necessary to help remove the metals from the body, this is where we take a compound that has a functional, like a sulfur which binds to the metal and helps it to be excreted out of the body and eliminated.

So those are the types of courses of action that you can take. And of course, if the child has been exposed and you know that, then you’re going to want to very carefully monitor their academic progress, and if necessity get them tutoring or whatever to help them keep up and get early interventions really crucial because academic problems that a child is experiencing that are unrecognized can quickly manifest into behavioral problems. It’s not uncommon for children struggling in school to also exhibit behavioral problems and if you don’t know that the cause of the behavior is related to the fact that their doing poorly in school you don’t put two and two together, you know that can be a problem too. So, parents have to be aware of what their children are doing, where they’re playing, what’s in their toys, and monitoring for these things. And then be aware of the symptoms, you know lead exposure in children is often also associated with colic. Right, so if your child is showing gastrointestinal problems that seem to be chronic and you have a suspicion, that can be a clue that somethings wrong.

HR: Does the average doctor know what lead batteries to get?

MR: I think, with respect to heavy metals the general screen for heavy metals is pretty common. But if you suspect that there’s an unusual compound, like a pesticide, like an organelle phosphate, or something like this or a carbonate that they might have gotten into to, the test for that are a little more specialized and not as many doctors are familiar with those and not as many doctors are familiar with the effects of chemicals in children. Other than that, we’re starting to see that developmental exposure in children to organelle phosphates can have consequences at levels that we might not be concerned with again in adults. So the developing brain is a very sensitive time and catching exposures early, removing children from the sources of exposures early and doing what we can to facilitate their acquisition of their math and language skills by tutoring them in whatever they need to keep them up with their class mates so they don’t get left behind and develop behavioral issues and other problems as a secondary consequence of struggling with their academic pursuits. Of course, that’s not to say that the chemicals can’t cause behavioral problems in and of themselves, they can do that as well, so we should be aware of that as well.

HR: Now are there specialists in this area?

MR: Yeah, there are developmental specialists who specialize in developmental neurotoxicology and I know that there are some, a women at U Mass who’s name escapes me right now but who’s a developmental neurotoxicologist. There are definitely people who specialize in developmental neurotoxicology. You can find most clinically trained neuropsychologists have a pretty good understanding, at least with respect to lead exposure in children.

Environmental dangers

HR: Well it sounds like it’s a lot more than lead, that’s for sure.

MR: Yeah, the environment is filled with potential things, and so, you know, the most important thing for a child during development is that as a parent, that you’re observing how their doing in school and whenever possible take corrective actions. You know, it’s almost like sailing a ship, you know you got to change track ones in a while to get them through the system. And the system is designed for a student who might not be struggling, and if the child is not identified as having a developmental learning disability, but develops a learning disability because of a chemical exposure, they would be in a mainstream class rather than maybe in a class where there was additional support and they would fall behind much more quickly because there would be nothing, there’s no safety net with them cause no one even knows that they’re struggling.

HR: I would assume there’s a higher incidence of neurotoxins getting into our children in the poverty areas. Would that be a correct assessment?

MR: Yeah, low income housing, living in densely populated areas, we know we have a lot of pollution, older buildings, which may not have had adequate lead abatement or lead is simply covered over, you know it may not be completely removed, it adds to the problem. Living near a superfund site, there’s certainly a lot of issues that come with socio-economic problems as far as exposure to these chemicals in a home rather than in an occupational setting that people encounter.

Tools to combat the effects

HR: Now other than remedial tutoring and other than discounting the neurotoxicant, what other tools does the family have to combat this?

MR: Not much, not much unfortunately. I mean of course legislative action is very important. You know I lobby I go down to DC, I’m going to DC with the Parkinson’s researchers with Michael J Fox again next month. And we talked to congress about our needs to study neurodegenerative diseases, and of course we’re all concerned about the role of environmental exposures to chemicals in children and in adults. You know, one of the long-standing hypotheses, with respect to neurodegenerative diseases is the two hip model where someone is exposed to chemicals when their young and then as they age, that prior chemical exposure interacts with aging to resurface with a greater risk for neurodegenerative disease later in life. So, there’s chemical exposures that may occur when we’re an adult that could unmask a late neurodegenerative disease. But there’s also the idea that these exposures can occur many, many years before and not manifest until years later or when they interact with aging and the genetics to lead to an increased risk for neurodegenerative diseases. So, we’re very concerned with this and I lobby congress and the bill is out there trying to eliminate paraquat and other neurotoxicants that have been implicated as risk factors for causing mitochondrial dysfunction implicated in neurodegenerative diseases.

HR: Well you know I think of my dad who passed away with Alzheimers and Parkinsonism and thinking about our old family gas station in Jersey City where he was the mechanic and my mother used to pump gas, we all kind of hung out there, you know, you wonder how much of it is, because it’s all going to be, end up being multifactorial. I’m sure there is a genetic component and an environmental component and the significant neurotoxicants, certainly I think I underestimated and so forth, which disturbs me all the more that there’s been so much emphasis on going at it backwards through the end result. It’s kind of almost like we all know what kind of food is good for us what kind of food is bad for us you don’t have to wait till after the heart attack to eat what’s good.

MR: Right, right. And in neurodegenerative disease we don’t do that, and the reason is that, you know, when you think about the heart, it’s a pump right. It’s pretty obvious what it does. It’s got an intake chamber, it’s got an exhaust chamber, it’s pretty obvious, but with the brain it’s very complicated and we don’t fully understand the mechanics of the brain. The brain; it has an energy system, the mitochondria. It has a transportation system, which are the neurofilaments that transport the things up and down the axons, right. It has the gatekeepers that keep things in and out of the cell, regulating ion flux in and out of the cell. It has a system to bring in big things like an elevator system to bring in big molecules through endocytosis and get those out by exocytosis. We know a little bit about the mechanics.

But we don’t fully understand how these interact on a neural network level. Where what’s going on in the brain stem, which is influencing arousal, translates into what’s going on further out in the brain, saying the hippocampus where the basal level of arousal may influence the activity in the hippocampus that facilitates the transfer of information from one brain region to another and how all of this interacts and communicates between regions to not only function normally but what happens when this system starts to malfunction. The malfunction maybe in the brainstem, but the read out maybe problems learning in memory because the energy and the level of arousal necessary to transfer information from the hippocampus to long-term storage in the neo-cortex is dysfunctional and that in turn may lead to other problems as far as those cells are doing, how they handle debris that are building up in the cells, you know when we sleep that a lot of the debris in the brain gets cleaned so if sleeping is disrupted, if the circuitry that’s going on in sleep and arousal is disrupted, the brain may not cleanse itself properly and what are you going to have but bioaccumulation of toxicants in the brain as a downstream ultimate event that’s really related to an overall dysfunction of energy metabolism of arousal and transmission of activity within the brain.

HR: Dr. Marcia Ratner where can our audience learn more about you.

MR: Yeah. So, I said I’m with Boston University Department of pharmacology here, and then I have my own consulting firm called where you can learn a lot about the interactions between chemicals and the brain, and their role in Parkinson’s, Alzheimer’s, Huntington’s and Lou Gehrig’s disease which I’m interested in. You can also look me up at the Boston University Department of pharmacology website. I’m the project manager of the entire department and a researcher and an educator here. And I think I’ve said before on Thursday nights I said before on Thursday nights I give a pro bono consult to anyone who wants to give me a ring and pick my brain. I’m happy to do that.

HR: Is there anything we have not covered that you would like to cover today.

MR: Well, people have the blog I wrote on the internet, they can find that there and read more about that. No, actually, this was kind of fun because we went off into my other hat which is what I do for research and touched on some of the other things I’m fascinated by, so I think we touched on a lot and hopefully the viewers will enjoy what we’ve talked about and will take that little ripple from what we’ve started here and talk to each other on the internet, on forums and really put forward novel ideas. Talk to their congressman. Talk to their children, who may be interested in science. Whatever we can do to contribute to the process as individuals is a powerful force, because the power of us all combined is huge.

HR: Dr. Marcia Ratner, Boston University School of Medicine and, thank you so much for being with us and we hope you’ll come back again real soon.

MR: You’re welcome Hackie. Nice to be with you.