My guest today is Dr. Hannah Stevens.
Dr. Stevens received an MD and PhD in Neuroscience from the University of Illinois.
Dr. Hannah Stevens leads the Psychiatry and Early Neurobiological Development Lab at the University of Iowa,
Carver College of Medicine. Dr. Stevens is a distinguished professor of psychiatry and holder of the Ida P. Haller Chair.
Her work leads groundbreaking research into the molecular and cellular foundations of early brain development,
and is pivotal in linking prenatal stress, environmental factors, and genetic influences on childhood behavior and the emergence of disorders.
With her focus on the critical periods of pregnancy and early childhood,
her research aims to revolutionize the diagnosis and treatment of conditions throughout the lifespan.
In addition, Dr. Stevens recently published a review paper in biological psychiatry titled,
Developmental Disruptions of the Dorsal Stryatum in Autism Spectrum Disorder.
This is an interesting area in the so-called basal ganglia, an area known for its rosin, various learning methods,
that cognate the functions and motor movements. The dorsal striatum receives inputs for the basal ganglia that in turn
recruits various other subcortical regions used to orchestrate downstream behaviors.
For those roles, this is a region of interest for autism.
And now, my conversation with Dr. Hannah Stevens.
Dr. Stevens, can you start with explaining to me about your medical journey and your background?
Absolutely. Well, let me tell a little bit about my interest in the brain and neuroscience,
and that includes how I was trained medically as well.
So when I went to college, I became fascinated with the idea that all our behaviors have these correlates underneath that occur in our brain.
And chemical signals and electrical signals have the capacity to help us think certain things or move in certain ways and make choices,
which was fascinating to me, and I just couldn't turn away at that point.
So I decided I wanted to learn more about the brain, and I went on to do graduate studies in the brain,
but at the same time, I wanted to be able to apply what I was learning to directly help people.
And I was fortunate to get into a program where you can train in science with a PhD and as a physician with an MD at the University of Illinois.
And I studied their specific ways that the auditory system helps us understand language and the auditory part of the brain, essentially.
And at the same time, I began to be trained as a physician and a doctor in training,
and I began to see that how people develop through their early part of their life is fascinating from just an experiential and how it affects people's lives perspective.
And at the same time, how the brain develops was also beginning to excite me as well and thinking about that.
So I wanted to, when I completed my training there, I wanted to go into a field where I could look at development of people's lives and people's brains.
And for me, that was training to become a psychiatrist and specifically a child psychiatrist.
And at the same time, then continuing to do research in an area that was really relevant to psychiatry and child psychiatry.
And that because there were so many unknowns in child psychiatry about what led people to have the problems they were having, what led children to have emotional or behavioral problems.
I wanted to start early and look very early at formation of the brain and think about how that might set up the brain to not work as well for a person.
And so I began to look at prenatal or embryonic brain development.
And then I've taken that from there, studying both how particular genes and differences in genes affect prenatal and embryonic brain development, but also how different environmental experiences or exposures in the prenatal period can change brain development.
And that has brought us here to this time when I've actually, way back then decided I really wanted to understand the brain.
I've now reached the point where I have gone beyond just thinking of the brain, which is already complex enough to understanding that prenatal brain development involves interaction of the brain with a lot of other tissues, and in particular with the placenta that supports the development of the entire fetus or embryo.
And we think is worth studying for understanding exactly how it influences the development of the brain.
That's not something now that I do as I practice as a physician, I practice as a child psychiatrist. It's certainly not something I do in my everyday life as a physician.
I don't think about the placenta when I'm trying to help children and adolescents with emotional or behavioral problems. But when I try to think about how we might prevent those problems, that's where the science gets me excited to try to think about if we understand the biology that's happening as the brain is forming prenatally, then maybe we can prevent some of the problems for the kids that I see.
I kind of like to rate things. I think I've constantly rate things. And I think for me personally, the number one thing with autism research ought to be the cause.
And there's so much that says the placenta or the embryo is where we need to direct more attention. So I was so fascinating with knowing that you have a history with the placenta.
What is the placenta's role on the embryo?
That's a great question and a great place to start. So the placenta is really that intermediate structure that is there, that mediates things being provided by the maternal environment for an embryo, and that embryo growing and putting together its brain and of course, all of its other parts that it
has to grow. So the placenta provides nutrients by actively transporting nutrients from a mother, the proteins, the carbohydrates, the sugars that a mother consumes are actively transported to the fetus, so it has the building blocks to actually start to grow and put together
cells. And it also provides a lot of guiding molecules that tell it in part how to put those things together, but that's only in combination with what's already happening in the fetus itself. The fetus has kind of its own blueprint and some molecules coming from the placenta can help guide it.
So things like hormones, things like growth factors. And then the placenta has a big role in modulating the provision of oxygen because all human life needs oxygen and so oxygen exchange is very important in the placenta.
And then the removal of things you don't need. So as anything grows, anything functions, it produces wastes, all the cells of the developing fetus produce wastes and those have to be eliminated through the placenta in part as well.
So the placenta also seems to have come developed to limit the exposure of the fetus to things that wouldn't be good for its growth. And there's interesting active transport mechanisms in the placenta to keep out foreign type molecules, things that aren't natural in the human
milieu, maybe poisons that a person like if we're thinking of way back during evolution, a person might consume poisons from plants or something like that and today, you know, chemicals or medications can be actively kept from the fetus by the placenta.
So that's another very interesting role at place.
Okay. So, explain to me how the placenta from mother to mother is that be different.
Because I'm very fascinated recently over the last maybe three months about even pre pregnancy, the mother preparing for pregnancy.
Absolutely. So the placenta is actually made up in part of mother's tissue.
Part of the uterus actually changes after an embryo implants and becomes part of the uterus so part of, I'm sorry, part of the placenta so part of the placenta is of maternal origin and then part of it also arises actually from the embryonic cells of the embryo initially.
And so it has unique qualities that neither the mother nor the the offspring have in some ways because it's both of their tissues working together.
So it actually is, it's not just that it varies mother to mother but every time a mother has a new offspring or different offspring that placenta will be different that time.
But there are key elements that seem to co occur. So, for example, a problem in pregnancy that can happen to some people is that they'll develop a pregnancy specific disease called preeclampsia which makes the mother have high blood pressure and causes some problems with growth for the fetus and that's thought to the placenta is
a problem to play a major role in that a mother will be at risk if she has preeclampsia the first time she has a pregnancy. She'll be at risk the next time she has a pregnancy so there's some things that are kind of the same as the first time, but she isn't guaranteed to always have preeclampsia the second time
So there are things that are the same and things that are different.
Are you familiar with nerve nerve neuro factor in K no in F KB.
Yes.
Okay, could you tell me a little bit about that because I planned on doing a solo episode. And that might have been a large part of it. But if you can share, then that's data directly to me instead of my interpretation.
Oh, well yeah.
What got you interested in NFKB.
The roles of this time or this little epoch that we're talking about. And the roles with like DHA and omega three kind of maybe rescuing that.
So it was just, I just can't get enough about this air of this timeframe and knowing or trying to understand when does autism actually develop on that timeline from conception to birth.
Yeah, so I mean that's a really like we can step out and take that big picture view first before we go into the details of the molecule but the big picture view being that so everything that people have observed about autism is that as early as we can know what to look for we're seeing the
changes of autism in people who have that and suggesting that you know people used to think well is it a problem that occurs because of something that happens in early childhood and people are becoming more and more convinced that it actually occurs before early
childhood during prenatal development and some of the genes that have been associated with autism have pointed in that direction because they are genes that matter a lot for the development of the brain prenatally.
Not to say they have no role at other times also but that they're just so critical at those early time points that makes it seems like the way that the evidence would suggest it's happening before someone is born and then we start to pick up signs of it as a child develops further
and further skills or or they don't develop those skills sometimes that's what we see.
So, getting at this particular molecule so NFKAP-beta is a molecule that plays a big role in lots of different processes inside cells of all kinds so it plays processes it plays a role in cells of the developing brain, but it also plays a role of cells of the placenta and in fact seems to be one of the major factors
by which placental development itself is regulated so as the placenta develops it, it's a tissue that appears for this limited period of time, the period of pregnancy and it has to develop quickly and build itself quickly and then it's done.
And so it uses molecules like NFKAP-beta to form blood vessels and re-engineer tissue around those blood vessels and monitor the right level of sort of tissue creation and tissue part of development of any kind of tissue destruction because you have to have the right structure
and the right time set means sort of chipping away if you will kind of like that on a on a sculpt on a sculpture or something like that.
So NFKAP-beta through its major regulation of internal cellular processes is really important for all of those structures forming in the placenta.
So I can't remember his NFKAP-beta been suggested to be an autism linked gene. Is that one of the reasons you're interested in it, Ryan?
I'm pretty confident in saying yes, but I do have a tendency of because of, you know, I don't want to make this sound bad but sometimes we're faced with the different silos.
So this discipline can figure out something, but this one, it doesn't quite conceptualize that or integrate it.
So it might have been from that, but I think it's data does show that it is info.
I think, yeah, it rings a bell for me that it is. And I think one of the interesting things for us to start thinking about a lot of people as we just talked about have been looking at autism genes for how when do they play a role in brain development?
And they pointed towards all these prenatal phases of brain development.
And one of the interesting things since we're on the topic of the placenta that's starting to be discussed is what is the role of these genes not just in the brain?
We think of autism as a brain disorder, but also in structures that support brain development like the placenta.
So does, you know, we just discussed how NFKAP-beta has a very important role in the placenta.
And so one hypothesis that is an interesting one that some people are starting to explore is the risk for autism like problems arising not just from a role of a risk gene in the brain,
but in combination with the fact that that risk gene also affects the placenta, the two things happening together.
We've been doing some work not on NFKAP-beta, but on another autism risk gene or risk genetic risk, which is a copy number variant called 16P11.
Have you heard of that, Brian?
I've heard of 16P11.
Yeah, exactly.
Yep.
That's right.
So that's either a deletion of a part of a chromosome or a duplication, and it's associated with a higher risk of having autism or other neurodevelopmental problems.
And we have worked with a group at the University of Iowa that has a mouse model of that copy number variation and have found that the placenta of that mouse model is not like a typical placenta.
It just seems structurally different, and it seems to be functionally different.
Like it's sending different hormones and growth factors to the fetus.
And one of the most interesting things is that the placenta in general is really different in males and females.
And it seems that this risk gene, at least in this particular instance, seems to affect male placenta more than it affects female placenta.
And so in 16P11, it affects 16P11.2, affects both boys and girls.
They both have a risk for neurodevelopmental disorders if they have that genetic problem.
But there are some problems that arise in that disorder that are more severe for boys.
And so this is one possible source of that difference between boys and girls that might arise from the placenta being different in boys and girls.
Oh, wow.
That's, yeah, that's very fascinating stuff.
Oh, yes, it keeps us, every new discovery just makes us ask even more questions.
Yeah, it just provides information about, you guys have no idea what's happening.
Sometimes it feels that way.
Yeah, yeah.
And that wasn't a shocking issue.
I'm just saying, overall, okay, there's this now.
Yeah.
You mentioned oxygen earlier, and also I wanted to talk about the tissues too, because something else that's, I'm always fascinated with, because if it's autism, there's autism and I call it XYZ.
There's so many comorbids going on with the tissue, something that whenever I saw this data, I was like, oh my gosh, autism and leukocytes.
And I was like, what is, what is the connection there?
And as you described the tissues and so forth, I'm just wondering if, if you have any insight into that, if not, that's fine too.
That's, that's, we could probably talk a lot about that.
I'm wondering, are you wondering, are you thinking about leukocytes during prenatal brain development, or are you thinking about leukocytes in general?
I'm just thinking in general, but everything that I, as, as I discover or come across, I, I bias towards this timeframe that we're talking about.
Yes.
Well, it's interesting because one of the things you might know about pregnancy and prenatal development is that because the tissue of the fetus is different than the tissue of the mother, the immune system of the mother could have a reaction against the fetus.
And one of the major things that sustains pregnancies is that there's an immune shift during pregnancy so that there isn't rejection of the, of the fetus.
And obviously, leukocytes are white blood cells, which are a part of the immune system and allow us to fight disease and clean up stuff that's not supposed to be there.
And they do seem to have, they do seem to function differently in pregnancy and they do populate the placenta.
And they populate the placenta both from the maternal side.
So mom has white blood cells that play a role in placenta and regulating the functions of the placenta.
And then the fetal white blood cells also start to develop, not they're not there right at the beginning, but they start to develop and also will play a role on the, on the fetal side of the placenta.
And immune perturbations during pregnancy are thought to be one risk factor for neurodevelopmental disorders, including autism spectrum disorder.
So I think leukocytes, we don't know enough yet, really, about all the ways they could be altering placental function, altering brain function.
But certainly the idea that inflammation is inducing a risk does mean that leukocytes have a role that we need to understand better.
Okay.
And you know, I mean, leukocytes are also a very interesting sort of window into the biology of a person because there's something that we can actually look at from the blood of a person.
We can't like take brain samples from people that just doesn't allow, you know, we can't do that.
But we can take leukocytes and leukocytes are thought to maybe sometimes have biology that allows us to understand other things that are happening in a person's body.
But there are limits to that because leukocytes are white blood cells and brain cells are really, really different than, than white blood cells. So.
Okay.
Do you know much about the brain development and things like cortisol or serotonin from the mother to the fetus?
Oh, yeah, those are two very interesting molecules during pregnancy for sure. Should we talk about those? Yeah.
Yeah, the serotonin one, it really captivates me because of how it's rolled and where it comes from tryptophan and the melatonin and serotonin right there in the biosynthesis and just serotonin is role in developing like the
sensory map of in the central nervous system.
Yeah, yeah, let's get into that. Yeah, absolutely. So as you've already pointed out serotonin plays a big role in putting together a brain that can detect stimuli that matter like sensory information.
Things like, you know, a map of like the where you where on the skin, you know, you might feel a stimulus or something like that.
And, you know, serotonin prenatally, so in general serotonin comes from parts of individuals own brain and can affect our like within my brain, I produce serotonin and it affects my brain development.
But there's a stage of development during prenatal life that the serotonin comes from the placenta. So this is actually one of the best explored aspects of how placenta and brain are connected in their development in that people have actually
manipulated in mouse models where we can understand this biology better placenta specifically in the in the serotonin specifically in the placenta and shown that that basically completely changes how the serotonin system develops in the in the
in the eighth offspring, because it relies on that serotonin from from the placenta. And so some of the idea behind the importance of the placenta for brain development is focused on babies who are born too early.
And then, while we become better and better at allowing and finding ways to support those babies to help them survive after being born early, one of the things we know is that we're missing a lot of the factors that the placenta produces.
While we are supporting their survival supporting their their development in many very, very important and positive ways, they, there are theories that missing things like the source of serotonin and the placenta is affecting the brain development of these prematurely born babies,
which is one reason why neurodevelopmental disorders may be more common in babies who are born prematurely it isn't just that they had a lot of stress because they do have a lot of stress, certainly because they have to be cared for so carefully and there's a lot of risks to them,
but it may be that we're lacking some of the key elements like serotonin coming from the placenta and there's another molecule and I know you had an interest in, in also in.
Oh my gosh I've blanked what was the other one you had said cortisol cortisol yes so you have but I would just want to mention before we get to cortisol that there is.
There's really amazing neonatology researcher at Columbia named Anna Penn, who coined this term neuroplacentology have you heard that before, right.
So, she coined that in the sense of how important the placenta is for the brain neuroplacentology is a field that she is very important and and she has shown that in her lab that another molecule called alopregnanolone is arises from the placenta.
Alopregnanolone is in that category of steroid hormones that cortisol is in and plays a big role in refining brain development, particularly in the cerebellum.
So, she is obviously interested in her and her clinical work she works with prematurely born babies. She's a neonatologist and is interested in the idea that perhaps providing some of the factors like alopregnanolone might assist brain development and that's one of the aspects of the work of her lab.
But it gets us into steroid hormones in general which cortisol is is one of the steroid hormones and steroids are very, very important for normal function. You didn't have steroid hormones, you know, your body really wouldn't function correctly.
But they also signal problems sometimes so cortisol is what's known as the stress hormone it becomes elevated in levels when a person is undergoing a lot of stress and does that so it can signal to the body.
Oh, you should now do the things that would help you deal with some stress you should, you know, release the glucose so we have some energy so if we need to run away we should do that you know it puts your body in a different state so it can it can respond to stress.
Of course too much stress can also be bad we all know that we don't want to experience too much. And during prenatal life, too much stress on the part of the mother, maybe a risk, it seems to be a risk factor through a lot of studies for neurodevelopmental disabilities in offspring.
That's not to say that the system hasn't attempted to, you know, I'm making it sound like an active player here but you know perhaps through evolution the system seems to develop so that too much stress hormone can't affect the offspring there are active functions in the placenta to
monitor how much stress hormone, how much cortisol is coming from the mother and convert it into things that aren't as that aren't going to cause problems for the fetus, but there are points at which that system is not as good it doesn't function as well.
And also stresses that cause so much of that activation and so much of that cortisol that likely it supersedes it overcomes those barriers.
And that's something my lab studies a lot of is the impact of stress on the developing offspring brain and we have found in fact that, you know, these studies in humans have suggested it's a risk factor for neurodevelopmental disabilities and we among other labs
have shown in fact that it causes specific developmental delays in the brain.
The first one that we had studied was a delay in the migration of cells that have to travel long distances in the brain.
And now we're interested in looking at other ways of understanding whether the brain gets delayed and and maybe stays in a period of growth for a longer period of time.
As perhaps one way of responding to cortisol or other factors that happen in stress so stress is a complex state and involves inflammation it involves cortisol, it involves changes in your cardiovascular function all of which might be part of the reason it is a risk factor.
Okay.
Cortisol. It often gets a bad it's a bit of a misnomer I think, because true we associated with stress so much but naturally it's what wakes us up in the morning.
So something is telling me that it's actually a good thing. We just maybe as modern humans kind of just don't know what it's supposed to be doing.
I think you're right. Yeah, exactly. I mean, then, you know, even at the, the phenomenological level we know that having absolutely no stress in your life isn't a good thing.
So even if we want to always put it together with stress, it would be bad for it to be gone entirely.
Yeah. And where it's cleared from in the hypothalamus is very telling. It's very fascinating, I should say, from pom-C, the ACTH, you know, the hypothalamus cleaves and then from the pituitary, the ACTH, but the ACTH in the clip hormone and then below that in this biosynthesis is a malano site.
So it's like, whenever we were discussing the leukocytes, I'm thinking about the aphomalano site as well, because of its role in leukocytes.
And these things are kind of like connected or are we just not doing what we're supposed to be doing with these molecules in these biosynthesis, because autism just kind of shows up in the 1930s.
So what really happened? What's changed?
Oh, that's such a good question. So many people are interested in understanding why we are describing more children now and maybe even beginning to describe them only 100 years ago or in not just children, people throughout their lifespan having these particular problems.
As with anything, I think there's a role for better understanding, leading people to recognize it more, right?
That the more we understand something and the more we feel like we have something that we can say about it or do about it, we will tend to notice it more.
But there's also the possibility that the rates have also changed. And that's, and it's hard to understand exactly why that would be. We know for sure that genetics plays a huge role in autism.
So, is it something that interacts with genetics? Is it something that's adding to genetics? These are all great questions that I don't think we have all the answers for.
And I don't know that much about melanocytes and leukocyte interaction. So I don't know that I can comment on that.
Yeah, yeah. Sometimes I just get excited.
Yeah, no. That'll be the next podcast.
Yeah, yeah.
There's always good to have more and more topics coming.
Yeah.
Let's talk about, well, there's two items here while we're on the placenta in this prenatal timeframe.
I'll just mention them both. But placenta's role in gene expression and DNA methylation.
And then also if you know anything about cell proliferation, then the differentiation and then you mentioned migration earlier.
You can just.
Sure, sure. Absolutely.
So placenta in terms of methylation. Well, so, I mean, in case your listeners aren't up on methylation, that's a way that the genes that are the same in everything.
Well, not every single, you know, in most of the cells of my body, I have the same genes, but they're doing very different things in different cells and they do very different things at different ages as well.
And we think that a lot of that regulation for how does the gene, the set of genes I have do something different in different scenarios comes from whether they're methylated or other modifications that are similar to methylation.
So not to put it all in the back of methylation, but it's not that methylation reflects developmental stage so that there's like normal changes in methylation that occur.
Like when are when we make gametes that are going to produce like an embryo when they when they join an egg and sperm.
There's methylation changes that occur through the division of the earliest cells of a of a of an embryo blastocyst stage.
And then there's also methylation that's thought to reflect exposures and sort of keeping almost like a way of the cell of keeping track of things that have happened to it historically.
And then there's and then there's also at a completely different level of the role of methylation is in the brain, very rapid changes in methylation, like when we're sitting here talking to each other are probably part of what's allowing us to build memories of what we're doing.
And so that's another place that DNA methylation plays a role but in the placenta. It is interesting how, just like with any cell the methylation pattern might be able to tell us something about how the system was functioning as well as what the system had experienced before and that's becoming a way for us to
possibly look at function of the placenta, but also sort of the history of the placenta because it's a tissue as we talked about earlier that has a role for the period of pregnancy and then it has another you know then we're done with it.
And like, and but some researchers are starting to collect samples of placenta from lots of different pregnancies so that we could maybe look at methylation among other things to understand better does the methylation of the placenta differ between people who eventually are diagnosed with autism
eventually diagnosed with ADHD, or, you know, anything else like perhaps even understanding other diseases such as obesity just because the placenta plays a role in so much. I mean, it's intimately involved in all of fetal development when some of these problems may begin.
So, I'm not sure if there was anything particular about about methylation that you had been thinking about Ryan.
I mean, anything in particular, I just know that it's pretty common in the literature. So, yeah, yeah.
About the only thing I really know about it is it takes a donor from methionine. It's, you know, often things in their biology have those cycles, and then it gets the donor to folate and then on from there.
Yeah, and so you're basically in part pointing out that methylation can't just happen just because we sell wants to have methylation has to have the right co factors there to actually make the methylation happen and that can also be a way that you can know if, you know, there's been perhaps a limitation of certain nutrients by virtue of methylation patterns.
But, but something else you said earlier.
Maybe Oh, we were talking about developmental processes of things like migration and proliferation.
And so, so, so in placenta, the cell, you know, making that tissue informing that tissue rapidly does involve those normal processes of cells dividing proliferating and cells migrating to where they need to go including cells that contain particular nutrients who that have to locate themselves
particularly in certain parts of the placenta so that they can provide the nutrients to the fetus. But the, I had referred to some processes like proliferation and migration with respect to the fetal brain, because the fetal brain has a very also very systematic way that it gets put together and that
involves cells being rapidly produced you have to produce thousands, tens of thousands of cells very quickly. And in fact, we don't produce really, for the most part, any more neurons after the prenatal period not to any large extent in very small numbers is there are
new neurons produced. So we get all of the neurons we're ever going to need to do all the stuff we're doing talking the thinking all this stuff, what in the prenatal period, and those cells are all born in sort of the, if you think of the developing brain, this is maybe
very, very simplistic, as sort of a donut shape it has a hole in the middle, and it's sort of a donut, and that hole in the middle is sort of the fluid filled space and all the cells that are born are born right along the edge of that hole and then they have to migrate away from that edge of the hole into
the rest of the donut. And so cell migration is a major phase of brain development that requires a lot of energy, because the cells have to move, and, and requires very, very specific guiding signals so the cells know where to move.
And some of those things we think were in the models that we looked at the migration of cells seem to be the cells weren't getting the right cues on where to go.
When they were in the presence of, of stress, maternal stress I should say. And we actually think that another way of describing another way of using the word stress is in a cellular context is oxidative stress and in first cells that's not the same as the kind of stress you and I as
people experience it's like a cell experiences an imbalance in the level of like damaging molecules, it gets exposed to, and we think that oxidative stress is playing a role in misdirecting some of that migration during prenatal brain development that that might also contribute to neurodevelopmental disorders.
The source of the oxidative stress is that from the mother or is that in the womb itself.
Yeah, I think it's, I think it's getting focused on the, it originates probably in some of the very specific aspects of maternal physiology that change in certain circumstance. Like we talked about maternal stress can involve cortisol, it can involve inflammation and those processes.
When directed at particular cells like the cells of the placenta the cells of the fetal brain can actually then secondarily induce oxidative stress so it's, it sort of originates in the mother but it's filtered through the placenta and the fetal tissue response to those things that are happening from the mother.
And so we, we have found in some of our models that in part those effects can be blocked by antioxidants so people have heard of that probably because we hear about antioxidants in our diet and antioxidants are molecules that can combat oxidative stress.
And we have provided that in our models where we think there's a high level of oxidative stress occurring and this is causing a disruption of brain development we've found correction of some of those processes when the mother is given antioxidants to wall wall also experiencing the
risk of the risky condition that the stress condition. So, so that we do think that it's not at the level of an exact dose or an exact guidance in diet but we do think that it's good to have a good level of antioxidants in your diet during pregnancy just because it can help regulate some of the
keep in line in the normal range of operations the levels of, of, you know, oxidative stress, not allowing it to get to out of control.
I've seen some data saying that autism and mitochondria, there's about 80% implicated with mitochondria, but I'm like, I think that's highly misrepresented. I think it's closer, probably to 100% or maybe even 100%
Yeah, yeah, I don't I don't know about the percentages but I mean there are some theories that part of the problem is in mitochondrial regulation of providing energy and then cleaning up the byproduct of producing that energy which is cleaning up the oxidative stress so
I mean it is a very interesting idea and there are some there are some very specific genetic deficits in that process that are that cause neurodevelopmental disabilities.
It does show us that for sure that problem can result in in, you know, a problem like autism, but you know I don't know the extent of it across all different people who have autism.
Yeah the mitochondria. It's a bit of a bad word right now, but it's for a good reason I think.
It's important. So, yeah, there's so many of them though. So it's kind of hard to dial in. It's easy to look at the role of one, but like the cell nucleus there's so many. How many does it take.
How many abnormal mitochondria in a cell, nucleus does it take for the cell to kind of underperform.
Very good question and it really probably depends on what the cells trying to do. Stage of development, all the other things going on at the same time that's why biology so interesting yet so confoundingly complex.
Yeah, whenever you mentioned oxygen earlier I instantly went to mitochondria.
And Richard Fry was on and he said this nonchalantly say the whole reason we breathe is so oxygen can function into cytochrome c-oxidase.
I love that. I love that. That's a great one.
I would never thought what we breathe so that reason in the mitochondria.
With even what we know about melatonin being produced in the mitochondria during the day. And then that maybe being, if we were to subordinate them, melatonin being our number one antioxidant.
Of course there are other crucial ones, but it's something like that.
The daytime environment, maybe even like as being removed from the sunlight now. And because of the electrons.
Are we deficient on electrons.
Oh, so you're thinking about like changes in modern life as we have and the rates of autism going up and less sun exposure.
That's interesting. That's interesting. I would now would say that like there's so many things contributing to
changes in the provision of certain molecules. I, you know, modern diet major major shift right like we eat so differently than we did 100 years ago.
So that's another one but yeah that's a very interesting hypothesis.
I'm, I'm, I'm hitched on it though Dr Steven so I just have to caution you that autism predates all of these other environmental toxins that are discovered now.
I'm not saying that they're not important, but the artificial light predates autism.
And then light is, if we think about quantum physics, light is electrons.
It doesn't have it hits matter. And then you know it, this causes so much energy to come about that.
And we've neglected ourselves and I think maybe that's why autism shows roughly two generations after artificial light.
That's interesting. There is, there is a field of biology called quantum biology. I don't know if you've heard of that where people try to understand the role of quantum particles in the processes of cells which is really a, I starts to blow my mind
even more than most biology does.
Yeah, this is as far upstream in the cell as you can go is quantum biology because it's what drives biochemistry biochemistry doesn't work without those that the quantum physics the signals from the environment is, is what I'm taught.
Yeah.
Yeah, but
Big ideas. Wow.
I can't comment. I don't think autism or origin. It originates in the 1930s and the rates also follow us, removing ourselves more from the sun and introducing artificial light and the types of artificial light, because light has a wavelength.
I wonder how, you know, with these disorders that are that are so modern that have modern definitions.
I wonder if we, how we would ever be able to determine if people did have these problems before.
You know, you do see characters in literature that was written hundreds of years ago that appear to have some of the issues of modernly defined neurodevelopmental problems, particularly think about ADHD in that way.
And in historical record, there's quite a bit of reference to people who struggle with attention and control of movement and things like that but we, you know, getting a rate would be so hard, a real rate.
It's always going to be a bit of a mystery to know how much it was, you know, happening 100 years ago and then, you know, the social, the cultural response to it too is like, maybe people were even, you know, there's more stigma maybe in the past.
So maybe people didn't even have a chance to know people who might have had autism. I don't know.
Yes, to think about ADHD goes back a couple of hundred years, 17th century maybe. And our modern environment environment doesn't do it any favors.
So that's true. All the distractions are pretty tough. Yep. Yeah. Yeah. Yeah.
For sure.
We haven't even talked about the dorsal striatum. I know we haven't, but we've already been talking a long time.
Yeah, that's okay. But I do have a couple of questions for you before we wrap up. Sure.
I love the dorsal striatum so much. But I realize we're not going to get into it but I am very curious about what are you recently most excited about?
Are you personal or professional in your research?
Yeah. So we, you know, well, since you've alluded to the dorsal striatum, I will say we have some really interesting data.
So one of the things to think about if we're trying to understand how prenatal events and brain development influence the risk for neurodevelopmental disorders,
the major factors that happens is determining the right size of a structure and the right cellular population that goes into that structure.
And so we've been interested in that from the sake of the dorsal striatum. Many, many people have focused on that question from the standpoint of the cerebral cortex.
So there's been a huge range of literature going back 20 years on what regulates the right number of cells populating the cortex and people have studied genetic factors and they've studied environmental factors and have, you know, emphasized the role of these wonderful cells, the microglia in regulating those processes,
but not as much as really been done about how do we regulate the right size of the dorsal striatum. And because of evidence in the literature that autism seems to have enlarged dorsal striatum from the earliest time point that people look at brain imaging studies of people with autism,
we wanted to understand what if we try to manipulate the size and the cell population that goes into building the striatum. And so we have really new data that we're just going to present this coming week and is still really being collected,
showing that if we use a modulator of cell proliferation in mice while their brains are developing in utero,
we actually seem to be able to increase the size of the striatum and disrupt some of the kinds of problems that are some of the kind of behaviors that are also disrupted in neurodevelopmental disorders including things like habit learning or procedural learning,
which the striatum plays a huge role in is allowing us to learn how to do things in a very regulated patterned way just so we don't have to think about it every single time we do something.
So we have new data suggesting that when we, when we manipulate this and grow the striatum beyond the point where it normally will grow that we see this disruption of these procedural learning behaviors in the animals after they grow.
And that they're the one thing we really want to understand is, what is that what happens when we increase that growth early, does it stay increased, does it actually get even larger over time because one of the other phenomena in autism is that the
dorsal striatum doesn't just begin larger, it actually seems to grow faster through childhood. And so we will, we want to look at this model, if we really have been successful in creating it and understand how it tracks over time and how it changes with development because we think
that might help us understand some of the places where you could, maybe you can't change the initial events that occur prenatally because you don't yet know that you have the issue, but could we find out how it tracks with time, and then find ways to, you know, if a person is having a big problem because
of the symptoms, find ways to modify the stradle, the stradle cells, the stradle structure in ways that would be beneficial. So that's that's really an exciting thing for us right now.
That is exciting. Do you know if it's the larger sizes, increased amounts of dintrites and axons and even the morphology of it.
Yes, that's one of the questions we want to find out. So thus far we've really been, we've been focusing on creating more of the cells that build the structure, because we see those differences in people with autism.
And it seems to just that it's an early fundamental problem like the cell population, but it might lead to this to what you're saying also that you have alterations in dendrites and synaptic structure and that would be something we have to explore after we after the next stage of the study, it's coming right up.
So yeah, hopefully we'll be able to answer that question soon.
Yeah, I'm looking forward to that. It makes kind of makes sense because it's, then those areas become preferred because our central nervous system just wants to respond. It doesn't like to work.
It just wants to respond based off of what it knows.
Right, right. Yep. Yep. Yeah, and I mean that would suggest, you know, we know that even if we don't necessarily see increased structure in people with autism, we know that straddle connectivity to the sensory cortex is also more than in people in people who don't have autism.
So we have like the cells not only maybe in some people there's more of them but maybe in other people it's not that there's more cells is that they're just more active. And, you know, understanding why that would be would be another would be another goal.
Maybe that's you know, when we see these things happen in people we don't know for sure if it's like a, that was part of the thing that caused the problem or is that actually what the person is doing to try to deal with the problem.
You know, that's still up for interpretation but certainly worth exploring.
Yeah, that's awesome. Well, Dr. Stevens, I just loved our conversation and I thank you for your time.
I'm looking forward to the data you just explained and I'll be looking out for it.
Oh, fantastic. Well, I'll keep you updated for sure.
Yeah, please do.
That would be great. That would be great. Well, thank you so much for all your interest in the in the placenta. I, you know, I'm really hopeful that the big take home point is I'm just hopeful that we can do the right thing to support healthy brain development as much as
possible as early as possible and that really all starts by, you know, making sure we know what goes into a healthy brain in the earliest time points so that's my that's my goal.
That's awesome. That's my number two on my list number one's cause and number two is identification and early biomarkers because this is undisputed that the earlier the better.
Well, thank you. Have a great weekend and thank you so much. Yeah, take care.
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