March 10, 2025 • 39 mins
For today's episode, we go into the science of embryogenesis, focusing on neurulation—the critical process where the neural tube forms, laying the groundwork for the central, peripheral, and enteric nervous systems. We discuss how disruptions in this early developmental stage, influenced by factors like folic acid metabolism, the sonic hedgehog pathway, and genes such as PTEN (P10), could shape the autistic phenotype. From cell proliferation to migration, we connect these biological processes to autism, exploring how environmental factors—like a pregnant mother’s exposure to artificial light versus sunlight—might alter developmental outcomes. This episode sets the stage for when the Autistic phenotype begins and for more detail on why the mesencephalon does not evolve into other cell types like the other three areas (prosencephalon, rhombencephalon, and spinal cord).
Daylight Computer Company https://daylightcomputer.com
use "autism" in the discount code for $25 coupon.
This is the future of tech.
0:00 Daylight Computer Company
4:20 Neurulation; primary & secondary
6:26 Neural tube, MTHFR & Folate (Vitamin B9), DNA methylation
11:51 Neuroepithelial Cells; Neural Crest, Surface Ectoderm, Mesodermal
16:05 Environmental implications, proliferation, differentiation, and migration
18:45 PTEN
26:29 Modern Environments
28:00 What do you think light is? Autism is in the Womb
31:40 Hyper and Hypo-connectivity
34:40 some rants
35:51 Leo Kanner kid, Donald Tripplet; The Biology that gives us Autism allows us to be comfortable within ourselves; more rants, probably
37:59 Review/Ratings & Contact Info
Hopp: https://www.hopp.bio/fromthespectrum
YT: https://www.youtube.com/channel/UCGxEzLKXkjppo3nqmpXpzuA
email: info.fromthespectrum@gmail.com
Mark as Played
Transcript
Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
(00:00):
I would like to take a moment and mention a pressing issue we are seeing in our modern
(00:06):
world.
And that is tech use and tech light.
The data are impressive and concerning on isolated wavelengths of light, especially shorter
wavelengths, which is blue light.
(00:28):
For those that don't know, we have chromophores, which are special proteins that absorbs specific
wavelengths of light.
For blue light, the light that is LED light and tech light, that protein is called melanopsin.
(00:48):
Melanopsin is responsible for our circadian biology, physiology and cell functioning.
Hormone regulation and even a connection to an area huge for mood.
A consideration we should include is this protein was not even discovered until 1998.
(01:15):
It seems important for us to understand how our biology uses the different wavelengths
of light for various aspects of our biology.
This blue light chromophore is our master controller, our master clock.
(01:37):
Remember circadian rhythm is a two part process, two independent parts, light and dark.
Very quick reference, see the 2017 Nobel Prize in Physiology and Medicine.
But for now, I have something exciting.
(02:00):
I want you to introduce a product unlike any other product available.
A highlight is the product from Daylight Computer Company created their product based
on these factors.
The Daylight Computer is completely blue light free.
(02:20):
It has no flicker, short wavelength flicker is extremely harmful for our eyes and downstream
biology.
Light flicker is constantly turning our central nervous system on and off.
Essentially, it is like going to a light switch and repeatedly turning it on and off.
(02:43):
The problem is blue light and LED light does this and it is so rapid you cannot even perceive
this in real time.
The Daylight Computer is the lowest stimulation and foremost for sensory sensitive users.
(03:05):
It is no question that the alternative product especially when used at night do not adjourn
or dress or consider this in their product.
It is so toxic to human biology, big tech corporations have patents on how their short
(03:25):
wavelength implicates the human nervous system.
And a bonus, despite Daylight Computer not having backlight, it is very functional for
outdoor use and of course, increased sunlight is always preferred.
(03:46):
I am happy to offer a discount for the Daylight Computer.
You can use the code AUTISM for a $25 off coupon.
Again, use the code AUTISM and the discount code for $25 off.
See the link in the show notes to Daylight Computer Company or just give it a quick search
(04:11):
in your internet browser.
Use the code AUTISM for $25 off.
For today's episode, we will cover how the central nervous system is developed.
We will cover parts of embryogenesis.
(04:32):
So we will cover the developmental parts of the peripheral and enteric nervous system
as well.
All three, the central, peripheral and enteric nervous system are crucial for understanding
the autistic phenotype.
(04:52):
We will cover how the living organism is developed from the neural tube, the crest and neural
lation, neural epithelial cells and so forth.
The purpose is to cover these early phases of brain, spine and body development.
(05:17):
We will cover this in two episodes because I want to get to more details on why the
mesencephalon does not evolve into larger biology like the other cell types.
Neuralation is a very fascinating stage that happens in early development.
(05:42):
This starts with the formation of the neural plate, a flat sheet of ectodermal cells on
the embryo's dorsal surface.
This typically kicks off around about the third week of human embryonic development.
And neural lation can be broken down into two main phases, primary and secondary.
(06:09):
For the primary phase, there is a neural plate formation.
And then it begins to take shape and it folds.
It folds inward.
And the fold eventually meets and fuses at the top.
And this creates a hollow tube.
This is the neural tube.
(06:30):
This closure begins near the middle of the embryonic stage, typically within 22 to 28
days of the development.
Now once this is fused, the neural tube will detach from the surface and then close in
order to form the skin.
(06:51):
So this front end of the tube will eventually make the brain while the rest of the tube
creates the spinal cord.
So what's fascinating here, because we've covered this in many episodes, at this
point, also the peripheral nervous system is being developed and the facial cartridge.
(07:16):
And here's the part, pigment cells.
Pigment cells are already on the scene.
The secondary neural lation, and this happens at the lower part, the coddle part, the tail
end of the spinal cord, and cells clump together, the mesoderm clump, and this will create the
(07:39):
rest of the spinal cord.
So why this matters is neural lation sets the stage for the entire central nervous
system.
Major defects here, if that tube doesn't close, is spinal bifida, not necessarily our topic,
but our topic is also crucial here, because this closure will determine how the brain
(08:06):
development occurs.
At each stage, it's important for the process to complete.
A region of interest here already is folic acid is very important, and you know, if you're
paying attention to autism research, folic acid, vitamin B nomin, is heavily researched.
(08:30):
In fact, Richard Fry was on talking about Lycoborin and his research assistant, Nicole
Renton, they've both talked about folic acid in quite detail.
In addition to the folic acid, there's a region of interest here called sonic hedgehog.
(08:51):
Not sonic the hedgehog.
We will get into more of that later.
But the vitamin B9, the folic acid, this is crucial during pregnancy.
For many reasons.
One reason is, it supports DNA synthesis and cell division, huge for the developing living
(09:18):
organism.
This is key for the rapid growth of the neural tube, and if the folic acid is off, it will
impact how the brain is developed, too low or too high.
The folic acid here can affect how the neural progenitor cells divide, migrate, or connect,
(09:41):
huge for autism.
If you followed along with the podcast or even autism research, autism research does
a pretty good job here of the folate metabolism.
There is a popular enzyme here, M-T-H-F-R.
It's almost like motherfucker gene.
(10:03):
It's methylene, tetrahydrofolate reductase.
Remember enzymes end in ACE, ACE.
Again, it's methylene, tetrahydrofolate reductase.
(10:24):
This gene helps convert folate into a form that the body can use.
And if it's not working, the folate metabolism is abnormal and this will implicate the neural
relation and the brain development.
And that's what the concern is.
The DNA methylation, that's huge for folate.
(10:48):
And remember a previous episode when we talked about methionine gives a donor called SAM,
SA-M, to folate for this DNA methylation.
It's role here, it's not just the neural tube and this neural relation, it's also involved
(11:09):
in neurotransmitter synthesis.
Seems like serotonin and dopamine, those neuromodulators I should say, and the epigenetic regulation.
This turns off and on genes.
This is huge in autism.
So in addition, there's a neural crest and these cells, they pill off during the neural
(11:32):
relation and begin to form the enteric nervous system, one of the most common comorbid problems
for the autistic phenotype.
This is huge and this area, this timeline that we're talking about is a huge region of interest.
(11:52):
So with the neural relation, the formation will begin four different cell types.
These four cell types are neuroepithelial cells, neural crest cells, surface ectoderm
cells and mesodermal cells.
First, the neuroepithelial cells will break into four additional cell types and this is
(12:19):
going to be part of episode two of this little back to back series.
However, for now, the neuroepithelial cells, and this is the process of the neural plate
folding into the neural groove and then the neural tube.
We've already talked about this.
So once this tube closes and these cells form those progenitors of the neurons and glia cells,
(12:46):
so this is huge here because we're talking about neurons and certain glia cells like
astrocytes, remember the internal calculator with the neuroepinephrine from the locus serilius
and the astrocytes.
And we're also talking about oligo-dendrocytes here, huge for myelination.
(13:08):
This is huge for the central nervous system and the neural crest cells.
These cells emerge from the edges of the neural folds and this begins critical tissues here
for the peripheral neurons like sensory and automatic ganglia, okay, which is huge for
(13:29):
the body and movements.
Also here are Schwann cells, which are a further insulated myelination type of cell.
And the facial cartridge and bone, the adrenal, medulla cells, huge for our stress response
and our get up and go and a huge part here, a huge highlight right now.
(13:54):
Melanocytes, this is huge.
This is how the brain and body are connected.
Remember the melanocytes and the conversations about pom-C.
Remember the links to Dr. Jack Cruz and his Patreons from previous show notes.
A third type are the surface ectoderm cells and this is the skin layer.
(14:19):
This is the surface of the nervous systems.
The skin, hair, nails and even some sweat glands.
The fourth type is the mesodermal cells, which is where we could talk about the sonic hedge
hawk, but collectively the mesoderm signals to the ectoderm and it thickens into the neuroepithel
(14:46):
cells that form the plate.
This collection that I discovered, we are beginning to make the central nervous system
and as you learned, some of the peripheral and enteric nervous system, this is where
it's all connected or brain and body are connected.
(15:06):
And now if you think about autism and all of those comorbid, XYZ comorbid problems
like the GI problems and the muscle problems or any type of apraxia, the brain and body.
Why is this not a region of interest for us?
There are implications here.
(15:28):
Something is telling me this is a region of interest here, this little timeline that we're
talking about because remember the domino analogy, if the early processes, if the early
dominoes are off, all of the dominoes downstream are going to be off.
The process cannot continue properly.
(15:51):
So why the neuroepithelial cells?
Why this area?
Why this timeline?
Well with autism, it's not hard to find problems with cells dividing and migrating.
So the neuroepithelial cells are huge for proliferation and they divide symmetrically
(16:13):
to make more of themselves or asymmetrically to produce more neurons and glia cells.
And whenever this balance is off, there's too many neurons maybe or too few neurons
or too many glia, too few glia.
And this is huge in autism research and it's already established.
(16:33):
If you think about the episode when we covered the medial prefrontal cortex and this is huge,
the medial prefrontal cortex is a huge area for providing the living organism with adaptive
tools.
How's the organism, the living organism, going to respond in the environment to that stimuli?
(16:57):
The medial prefrontal cortex kind of leads the way.
Remember that in the Autism and Adaptive Responses episode.
And remember the episode on autism and the womb.
When we covered this, UC San Diego actually does a pretty good job of this.
(17:18):
There's too many cells in the areas of the medial prefrontal cortex.
So in addition to the proliferation and creating more cells, the migration and connectivity
problems.
This is very much aligned and very researched.
(17:38):
The data are very impressive here for autism.
Immigration and connectivity, neuroepithia cells give rise to radial glia.
And these are helping cells.
They act as scaffolds for the newborn neurons when we're proliferating and differentiating.
(18:00):
Remember cells should migrate to similar cells, friends flocked to one another.
And they use these scaffolding radial glia to migrate to similar areas and for the long
(18:22):
range.
Downstream connections, huge in autism.
So then let's talk about the signaling, these connections.
And this is huge here.
The sonic hedgehog, huge for the differentiation and the migration and two other areas, huge
(18:45):
here, huge in autism research is P10.
We've covered P10, probably episodes three, four and or five and shank three.
Episodes three, four and or five, but P10 here is huge.
(19:07):
P10 is phosphatase and Tinson.
Why does it matter for autism?
Well, P10 is a master regulator of cell growth, division and survival.
It's huge for tumors and cancer and the enlargement, brain enlargement, heavily seen in autism.
(19:31):
It balances these factors.
It makes sure the process and our biology here is within normal ranges.
If you think about P10's row with mTOR pathway as well, mTOR is huge.
Here are the episodes on Dr. Richard Frye and another episode that I covered.
(19:54):
MTOR complex one is a region of interest and a way to rescue the autistic phenotype.
Simply put, mTOR regulates cell metabolism and it is a region of interest for aging and
longevity science.
(20:15):
So some key rows of P10 outside of that.
Cell size and growth.
So two little P10 will equal bigger cells and an abnormal protein synthesis.
So if you think about the big brain, how autistics will typically have a bigger brain.
(20:38):
Eventually, they come back down to size, to normal size, but the children and even through
the womb, they have an enlarged brain.
P10 is a huge region of interest for this.
P10 also regulates synapsis formation and the plasticity, how neurons connect and adapt
(21:03):
and change through experience, neuroplasticity.
This is very huge, region of interest for autism.
This is all happening early on in this neuralation part, this embryogenesis already.
We know there are implications here.
(21:26):
And if you think about autism and the problems with the synapsis and that plasticity, P10
works hand in hand with AKT for signaling at the synapsis level and balancing, are you
ready?
Balancing excitation inhibition.
(21:46):
A very common scene with the podcast for explaining implications.
Remember the basal ganglia as well.
Remember the substantia nigra and how it sends excitation dopamine, D1 like, DR1 and DR5
(22:07):
for excitation and inhibitory dopamine, D2 like dopamine, DR2, 3 and 4.
We are going to cover this in great detail again because the substantia nigra is in guess
where?
The mesencephalon.
(22:27):
This is very critical.
But for the P10 with the migration, it's a huge problem for the migration and cell metabolism,
huge for autism.
It's linking the cellular energy.
It's a problem with the cell energy.
Remember the two episodes on the mitochondria, the solo episode and the one with Dr. Richard
(22:52):
Fry.
And lastly, because this is more than on the P10 than I anticipated, P10 helps regulate
the enteric neurons.
So the P10 and shank 3 are huge for this neuroepithelial signaling sensitivity.
(23:15):
And sometimes we've used postmortem studies.
We're going to do that again right now.
Pneumetaminesis studies of autistic brains show signs of early neuro over proliferation,
so more neurons in the cortex.
And this might start to understand why.
(23:35):
The neuroepithelial cells here are a region of interest.
There's a huge timing component here with the neuroepithelial and the folate metabolism
and the P10 and shank 3 and sonic hedgehog.
All of these things rely on critical timing.
All of these factors must be in sync.
(23:58):
We're always talking about timing and cell growth with autism, losing energy or having
a lack of energy.
And this is why this is the area.
This is the time.
This can cause the brain that structurally sound, that has no problems, become wired
(24:22):
differently.
So we're talking about those hypo and hyperconnectivities of the brain, even if the overall size is
not macroencephalic.
We can still have problems here because of these connections that are abnormal.
(24:42):
This sounds like autism.
And these factors are also huge for the peripheral nervous system.
So what does this mean?
How does the environment influence this of the embryogenesis and these neural relations
and neuroepithelial cells and so forth that we are discussing?
(25:05):
The environment provides context and will indicate how the mother and this womb and
the embryogenesis respond.
Neuroepithelial cells and environmental sensitivity is a very sensitive process here.
(25:26):
If you think about how the environment has changed, I've said this so many times, how
the environment of the mother has changed since autism was developed.
Remember the mothers of the canner kids?
I cannot overstate that.
I cannot overstate what the mothers of the canner kids looked like.
(25:51):
And think about the environment of the mothers now.
The mothers will just work up until almost birth indoors.
Maybe they are office jobs or school teachers or they work in factories.
Doesn't matter.
They are all indoors.
(26:13):
This is huge for the developing central nervous system, the peripheral nervous system and
the enteric nervous systems.
I cannot overstate this.
So what about these new environments?
Let's talk about the artificial light story and circadian disruption.
(26:35):
Humans before the artificial light and electricity, humans didn't have a problem here and there
was no autism.
But the impact on pregnancy, the pregnant mother circadian rhythm influences her hormones.
Things like melatonin and cortisol remember the early development of the adrenal medulla
(27:00):
cells.
This area comes on fast for the living organism.
And remember how fast the melanocytes are on scene.
This is connecting the brain and body.
These little developing living organisms in this time frame with the neural apotheosal
(27:26):
and the loss of energy here that are usually maintained for the developing organism.
Think about that disrupted circadian rhythm and how a lack of sun, the sunlight and that
power, the full spectrum and the lux, the amount of energy from the photons, the electromagnetic
(27:49):
strip.
Remember me asking repeatedly over the last six weeks, what do you think light is?
And is there a difference between the full sunlight spectrum and isolated artificial
light wavelengths?
And who is going to ask the question?
(28:11):
What does this look like?
What is happening here when sunlight hits skin and through the eyes of the pregnant mother
versus the artificial light?
And what is the environment of the mother now from 1930s from the mothers of the canner
(28:34):
kids all the way to 2025?
And what does the rates of autism looks like after we have switched our environment?
Why do people overlook this?
Why do they make it so complicated?
When nothing I've said we've covered today is complicated.
(28:58):
Cells proliferate and they differentiate and they migrate and cells are developed and the
mitochondria are environmental signals.
They need two things, oxygen and electrons.
(29:21):
How does that look like now in an indoor modern world?
What does that look like for the living organism?
And especially in a time where it's so sensitive and the central nervous system, the peripheral
nervous system and the enteric nervous system are being developed.
(29:47):
And show me one autistic example where the autistic does not have additional comorbid
problems with the peripheral nervous system or the enteric nervous system.
I will beg to offer, I suggest that every autistic person has an implication to the central
(30:14):
nervous system which is the easy one.
It's autism at its core is a problem at the central nervous system but show me one autistic
that doesn't have a problem with the central nervous system, the enteric nervous system
and the peripheral nervous system all three in one.
(30:35):
So let's look at the neuroepithelial studies.
This timeline here for the circadian biology there are animal studies that back this, this
prenatal light shifts alter brain development in animal studies.
In human data it's not so direct.
(30:57):
We won't go here but we know from studies from UC San Diego and the studies with the
machine learning from Dr. Ben Ari that came on, autism is in the womb.
It's not difficult here to predict autism in the womb anymore.
(31:22):
Downstream of this with the development of the autistic, maybe the child or young adult
even.
There are so many problems with migration.
The data are so impressive here.
Maybe there's a hyper connection and maybe some areas are hypo connected.
When do you think this occurs?
(31:44):
In neuralation and remember the domino example, neuroepithelial cells, this is the foundation.
This is where differentiation and migration is off.
Everything, the whole blueprint of the developing living organism with the central nervous system
(32:06):
and the enteric and peripheral nervous systems are going to be off.
With autism there are many mismatches.
There are many areas of the brain or the peripheral problems with motor control and the GI problems
in the enteric nervous system.
(32:29):
There are so many problems here.
With autism the hyper and hypo connections.
Let's talk about this with the over differentiation, the problems with differentiation here during
this timeline.
The neuroepithelial cells in the neural tube, the dorsal region of the neural tube, this
(32:50):
is the future cortex for the living organism.
This is very deep but this differentiation and these neurons are implicated here around
week six.
The cortical plate has extra neurons and spots.
(33:10):
For the temporal lobe this is vast for autism.
The over differentiation will have overpopulated local circuits forming dense, hyper connected
networks and childhood.
What this looks like for the autistic phenotype is this.
(33:33):
Hypersensitivity to sounds is what this means.
Remember the episodes on sensory processing.
Right here is when this is developed.
So hypo connections from the migration, failure.
So when the neural tube closes at around day 26, there is stress from the neuroepithelial
(33:58):
cells and they produce too few radio glia and it's misaligned.
Hypersmith for the frontal cortex gets stuck in deeper layers and migrate to wrong spots.
By month three, the prefrontal cortex lacks proper connections.
(34:22):
In addition, the parietal cortex where sensory integration occurs and the cortex here in
the parietal kind of orchestrate downstream behaviors based off of this.
And autistic children, autistic phenotypes of all ages, they lack the social ability.
(34:46):
They miss the social cues.
So what happens with the neuroepithelial cells in the ventral tube?
And this is where I want to stop because the ventral tube will eventually make the brain
stem, the mesencephalon.
And this problem here with the autistic phenotype and the developing embryogenesis because
(35:13):
folate is here.
I don't want to talk about folate too much next time, but for now since we've mentioned
folate, this shortage of neuron output will occur and these dorsal cells, this over-proliferation
implication, this brain stem area, this automatic area that the living organism uses to bias
(35:40):
our attention.
Remember the very first thing that Donald Triplett's father, the first child in the
Canner paper.
Donald Triplett, his father wrote over 30 pages documenting Donald's abnormal kind of
social withdrawn behavior.
(36:00):
And the first thing that Donald Triplett said, and I'm reading this directly from the Canter
paper right now, he seems to be self-satisfied.
He has no apparent affection when petted.
He does not.
Observe the fact that anyone comes or goes and never seems glad to see father or mother
(36:27):
or any playmate.
He seems almost to draw into his shell and live within himself.
Remember one of my biggest takeaways here with the whole podcast to explain the autistic
phenotype.
(36:49):
The biology that gives us autism allows us to be comfortable within ourselves.
It is no question.
It is undisputed.
It's not even a debate.
You can't even debate it that the autistic phenotype enjoys being within themselves.
(37:10):
These dreamlike states, the outside world is uninteresting.
Why I say that is, the biology creates us to be more alone, withdrawn from society.
Withdraw from the environment.
(37:30):
And I'm telling you, this is occurring from this early embryogenesis period.
Something is causing us to be abnormal.
And a large part is the migration problems.
What is causing the migration problems during embryogenesis and all the way through the
(37:52):
womb as the central nervous system is being developed.
If you are listening to the podcast, listening to the episode, please feel free to leave
a review or rating.
In podcasting, reviews, ratings and downloads are huge.
In Apple Podcasts, we have five stars.
(38:15):
Nothing but five stars, so I very much appreciate that.
Please feel free to leave more.
I would love your feedback.
You can contact me on x at rps47586.
We can have conversations about autism.
I'm always open and willing to have conversations about autism.
(38:37):
I am telling you, autism is the love of my life.
But remember what we just covered and how that should be easier to understand for you.
You can check out the YouTube page for all the full length videos and shorts and clips.
You can check out the Hoplink for links to all of the podcasts across different platforms.
(39:01):
You can email me info.fromthespectrum.com.
And thank you for listening to From the Spectrum Podcast.
I would like to take a moment and mention a pressing issue we are seeing in our modern
(00:06):
world.
And that is tech use and tech light.
The data are impressive and concerning on isolated wavelengths of light, especially shorter
wavelengths, which is blue light.
(00:28):
For those that don't know, we have chromophores, which are special proteins that absorbs specific
wavelengths of light.
For blue light, the light that is LED light and tech light, that protein is called melanopsin.
(00:48):
Melanopsin is responsible for our circadian biology, physiology and cell functioning.
Hormone regulation and even a connection to an area huge for mood.
A consideration we should include is this protein was not even discovered until 1998.
(01:15):
It seems important for us to understand how our biology uses the different wavelengths
of light for various aspects of our biology.
This blue light chromophore is our master controller, our master clock.
(01:37):
Remember circadian rhythm is a two part process, two independent parts, light and dark.
Very quick reference, see the 2017 Nobel Prize in Physiology and Medicine.
But for now, I have something exciting.
(02:00):
I want you to introduce a product unlike any other product available.
A highlight is the product from Daylight Computer Company created their product based
on these factors.
The Daylight Computer is completely blue light free.
(02:20):
It has no flicker, short wavelength flicker is extremely harmful for our eyes and downstream
biology.
Light flicker is constantly turning our central nervous system on and off.
Essentially, it is like going to a light switch and repeatedly turning it on and off.
(02:43):
The problem is blue light and LED light does this and it is so rapid you cannot even perceive
this in real time.
The Daylight Computer is the lowest stimulation and foremost for sensory sensitive users.
(03:05):
It is no question that the alternative product especially when used at night do not adjourn
or dress or consider this in their product.
It is so toxic to human biology, big tech corporations have patents on how their short
(03:25):
wavelength implicates the human nervous system.
And a bonus, despite Daylight Computer not having backlight, it is very functional for
outdoor use and of course, increased sunlight is always preferred.
(03:46):
I am happy to offer a discount for the Daylight Computer.
You can use the code AUTISM for a $25 off coupon.
Again, use the code AUTISM and the discount code for $25 off.
See the link in the show notes to Daylight Computer Company or just give it a quick search
(04:11):
in your internet browser.
Use the code AUTISM for $25 off.
For today's episode, we will cover how the central nervous system is developed.
We will cover parts of embryogenesis.
(04:32):
So we will cover the developmental parts of the peripheral and enteric nervous system
as well.
All three, the central, peripheral and enteric nervous system are crucial for understanding
the autistic phenotype.
(04:52):
We will cover how the living organism is developed from the neural tube, the crest and neural
lation, neural epithelial cells and so forth.
The purpose is to cover these early phases of brain, spine and body development.
(05:17):
We will cover this in two episodes because I want to get to more details on why the
mesencephalon does not evolve into larger biology like the other cell types.
Neuralation is a very fascinating stage that happens in early development.
(05:42):
This starts with the formation of the neural plate, a flat sheet of ectodermal cells on
the embryo's dorsal surface.
This typically kicks off around about the third week of human embryonic development.
And neural lation can be broken down into two main phases, primary and secondary.
(06:09):
For the primary phase, there is a neural plate formation.
And then it begins to take shape and it folds.
It folds inward.
And the fold eventually meets and fuses at the top.
And this creates a hollow tube.
This is the neural tube.
(06:30):
This closure begins near the middle of the embryonic stage, typically within 22 to 28
days of the development.
Now once this is fused, the neural tube will detach from the surface and then close in
order to form the skin.
(06:51):
So this front end of the tube will eventually make the brain while the rest of the tube
creates the spinal cord.
So what's fascinating here, because we've covered this in many episodes, at this
point, also the peripheral nervous system is being developed and the facial cartridge.
(07:16):
And here's the part, pigment cells.
Pigment cells are already on the scene.
The secondary neural lation, and this happens at the lower part, the coddle part, the tail
end of the spinal cord, and cells clump together, the mesoderm clump, and this will create the
(07:39):
rest of the spinal cord.
So why this matters is neural lation sets the stage for the entire central nervous
system.
Major defects here, if that tube doesn't close, is spinal bifida, not necessarily our topic,
but our topic is also crucial here, because this closure will determine how the brain
(08:06):
development occurs.
At each stage, it's important for the process to complete.
A region of interest here already is folic acid is very important, and you know, if you're
paying attention to autism research, folic acid, vitamin B nomin, is heavily researched.
(08:30):
In fact, Richard Fry was on talking about Lycoborin and his research assistant, Nicole
Renton, they've both talked about folic acid in quite detail.
In addition to the folic acid, there's a region of interest here called sonic hedgehog.
(08:51):
Not sonic the hedgehog.
We will get into more of that later.
But the vitamin B9, the folic acid, this is crucial during pregnancy.
For many reasons.
One reason is, it supports DNA synthesis and cell division, huge for the developing living
(09:18):
organism.
This is key for the rapid growth of the neural tube, and if the folic acid is off, it will
impact how the brain is developed, too low or too high.
The folic acid here can affect how the neural progenitor cells divide, migrate, or connect,
(09:41):
huge for autism.
If you followed along with the podcast or even autism research, autism research does
a pretty good job here of the folate metabolism.
There is a popular enzyme here, M-T-H-F-R.
It's almost like motherfucker gene.
(10:03):
It's methylene, tetrahydrofolate reductase.
Remember enzymes end in ACE, ACE.
Again, it's methylene, tetrahydrofolate reductase.
(10:24):
This gene helps convert folate into a form that the body can use.
And if it's not working, the folate metabolism is abnormal and this will implicate the neural
relation and the brain development.
And that's what the concern is.
The DNA methylation, that's huge for folate.
(10:48):
And remember a previous episode when we talked about methionine gives a donor called SAM,
SA-M, to folate for this DNA methylation.
It's role here, it's not just the neural tube and this neural relation, it's also involved
(11:09):
in neurotransmitter synthesis.
Seems like serotonin and dopamine, those neuromodulators I should say, and the epigenetic regulation.
This turns off and on genes.
This is huge in autism.
So in addition, there's a neural crest and these cells, they pill off during the neural
(11:32):
relation and begin to form the enteric nervous system, one of the most common comorbid problems
for the autistic phenotype.
This is huge and this area, this timeline that we're talking about is a huge region of interest.
(11:52):
So with the neural relation, the formation will begin four different cell types.
These four cell types are neuroepithelial cells, neural crest cells, surface ectoderm
cells and mesodermal cells.
First, the neuroepithelial cells will break into four additional cell types and this is
(12:19):
going to be part of episode two of this little back to back series.
However, for now, the neuroepithelial cells, and this is the process of the neural plate
folding into the neural groove and then the neural tube.
We've already talked about this.
So once this tube closes and these cells form those progenitors of the neurons and glia cells,
(12:46):
so this is huge here because we're talking about neurons and certain glia cells like
astrocytes, remember the internal calculator with the neuroepinephrine from the locus serilius
and the astrocytes.
And we're also talking about oligo-dendrocytes here, huge for myelination.
(13:08):
This is huge for the central nervous system and the neural crest cells.
These cells emerge from the edges of the neural folds and this begins critical tissues here
for the peripheral neurons like sensory and automatic ganglia, okay, which is huge for
(13:29):
the body and movements.
Also here are Schwann cells, which are a further insulated myelination type of cell.
And the facial cartridge and bone, the adrenal, medulla cells, huge for our stress response
and our get up and go and a huge part here, a huge highlight right now.
(13:54):
Melanocytes, this is huge.
This is how the brain and body are connected.
Remember the melanocytes and the conversations about pom-C.
Remember the links to Dr. Jack Cruz and his Patreons from previous show notes.
A third type are the surface ectoderm cells and this is the skin layer.
(14:19):
This is the surface of the nervous systems.
The skin, hair, nails and even some sweat glands.
The fourth type is the mesodermal cells, which is where we could talk about the sonic hedge
hawk, but collectively the mesoderm signals to the ectoderm and it thickens into the neuroepithel
(14:46):
cells that form the plate.
This collection that I discovered, we are beginning to make the central nervous system
and as you learned, some of the peripheral and enteric nervous system, this is where
it's all connected or brain and body are connected.
(15:06):
And now if you think about autism and all of those comorbid, XYZ comorbid problems
like the GI problems and the muscle problems or any type of apraxia, the brain and body.
Why is this not a region of interest for us?
There are implications here.
(15:28):
Something is telling me this is a region of interest here, this little timeline that we're
talking about because remember the domino analogy, if the early processes, if the early
dominoes are off, all of the dominoes downstream are going to be off.
The process cannot continue properly.
(15:51):
So why the neuroepithelial cells?
Why this area?
Why this timeline?
Well with autism, it's not hard to find problems with cells dividing and migrating.
So the neuroepithelial cells are huge for proliferation and they divide symmetrically
(16:13):
to make more of themselves or asymmetrically to produce more neurons and glia cells.
And whenever this balance is off, there's too many neurons maybe or too few neurons
or too many glia, too few glia.
And this is huge in autism research and it's already established.
(16:33):
If you think about the episode when we covered the medial prefrontal cortex and this is huge,
the medial prefrontal cortex is a huge area for providing the living organism with adaptive
tools.
How's the organism, the living organism, going to respond in the environment to that stimuli?
(16:57):
The medial prefrontal cortex kind of leads the way.
Remember that in the Autism and Adaptive Responses episode.
And remember the episode on autism and the womb.
When we covered this, UC San Diego actually does a pretty good job of this.
(17:18):
There's too many cells in the areas of the medial prefrontal cortex.
So in addition to the proliferation and creating more cells, the migration and connectivity
problems.
This is very much aligned and very researched.
(17:38):
The data are very impressive here for autism.
Immigration and connectivity, neuroepithia cells give rise to radial glia.
And these are helping cells.
They act as scaffolds for the newborn neurons when we're proliferating and differentiating.
(18:00):
Remember cells should migrate to similar cells, friends flocked to one another.
And they use these scaffolding radial glia to migrate to similar areas and for the long
(18:22):
range.
Downstream connections, huge in autism.
So then let's talk about the signaling, these connections.
And this is huge here.
The sonic hedgehog, huge for the differentiation and the migration and two other areas, huge
(18:45):
here, huge in autism research is P10.
We've covered P10, probably episodes three, four and or five and shank three.
Episodes three, four and or five, but P10 here is huge.
(19:07):
P10 is phosphatase and Tinson.
Why does it matter for autism?
Well, P10 is a master regulator of cell growth, division and survival.
It's huge for tumors and cancer and the enlargement, brain enlargement, heavily seen in autism.
(19:31):
It balances these factors.
It makes sure the process and our biology here is within normal ranges.
If you think about P10's row with mTOR pathway as well, mTOR is huge.
Here are the episodes on Dr. Richard Frye and another episode that I covered.
(19:54):
MTOR complex one is a region of interest and a way to rescue the autistic phenotype.
Simply put, mTOR regulates cell metabolism and it is a region of interest for aging and
longevity science.
(20:15):
So some key rows of P10 outside of that.
Cell size and growth.
So two little P10 will equal bigger cells and an abnormal protein synthesis.
So if you think about the big brain, how autistics will typically have a bigger brain.
(20:38):
Eventually, they come back down to size, to normal size, but the children and even through
the womb, they have an enlarged brain.
P10 is a huge region of interest for this.
P10 also regulates synapsis formation and the plasticity, how neurons connect and adapt
(21:03):
and change through experience, neuroplasticity.
This is very huge, region of interest for autism.
This is all happening early on in this neuralation part, this embryogenesis already.
We know there are implications here.
(21:26):
And if you think about autism and the problems with the synapsis and that plasticity, P10
works hand in hand with AKT for signaling at the synapsis level and balancing, are you
ready?
Balancing excitation inhibition.
(21:46):
A very common scene with the podcast for explaining implications.
Remember the basal ganglia as well.
Remember the substantia nigra and how it sends excitation dopamine, D1 like, DR1 and DR5
(22:07):
for excitation and inhibitory dopamine, D2 like dopamine, DR2, 3 and 4.
We are going to cover this in great detail again because the substantia nigra is in guess
where?
The mesencephalon.
(22:27):
This is very critical.
But for the P10 with the migration, it's a huge problem for the migration and cell metabolism,
huge for autism.
It's linking the cellular energy.
It's a problem with the cell energy.
Remember the two episodes on the mitochondria, the solo episode and the one with Dr. Richard
(22:52):
Fry.
And lastly, because this is more than on the P10 than I anticipated, P10 helps regulate
the enteric neurons.
So the P10 and shank 3 are huge for this neuroepithelial signaling sensitivity.
(23:15):
And sometimes we've used postmortem studies.
We're going to do that again right now.
Pneumetaminesis studies of autistic brains show signs of early neuro over proliferation,
so more neurons in the cortex.
And this might start to understand why.
(23:35):
The neuroepithelial cells here are a region of interest.
There's a huge timing component here with the neuroepithelial and the folate metabolism
and the P10 and shank 3 and sonic hedgehog.
All of these things rely on critical timing.
All of these factors must be in sync.
(23:58):
We're always talking about timing and cell growth with autism, losing energy or having
a lack of energy.
And this is why this is the area.
This is the time.
This can cause the brain that structurally sound, that has no problems, become wired
(24:22):
differently.
So we're talking about those hypo and hyperconnectivities of the brain, even if the overall size is
not macroencephalic.
We can still have problems here because of these connections that are abnormal.
(24:42):
This sounds like autism.
And these factors are also huge for the peripheral nervous system.
So what does this mean?
How does the environment influence this of the embryogenesis and these neural relations
and neuroepithelial cells and so forth that we are discussing?
(25:05):
The environment provides context and will indicate how the mother and this womb and
the embryogenesis respond.
Neuroepithelial cells and environmental sensitivity is a very sensitive process here.
(25:26):
If you think about how the environment has changed, I've said this so many times, how
the environment of the mother has changed since autism was developed.
Remember the mothers of the canner kids?
I cannot overstate that.
I cannot overstate what the mothers of the canner kids looked like.
(25:51):
And think about the environment of the mothers now.
The mothers will just work up until almost birth indoors.
Maybe they are office jobs or school teachers or they work in factories.
Doesn't matter.
They are all indoors.
(26:13):
This is huge for the developing central nervous system, the peripheral nervous system and
the enteric nervous systems.
I cannot overstate this.
So what about these new environments?
Let's talk about the artificial light story and circadian disruption.
(26:35):
Humans before the artificial light and electricity, humans didn't have a problem here and there
was no autism.
But the impact on pregnancy, the pregnant mother circadian rhythm influences her hormones.
Things like melatonin and cortisol remember the early development of the adrenal medulla
(27:00):
cells.
This area comes on fast for the living organism.
And remember how fast the melanocytes are on scene.
This is connecting the brain and body.
These little developing living organisms in this time frame with the neural apotheosal
(27:26):
and the loss of energy here that are usually maintained for the developing organism.
Think about that disrupted circadian rhythm and how a lack of sun, the sunlight and that
power, the full spectrum and the lux, the amount of energy from the photons, the electromagnetic
(27:49):
strip.
Remember me asking repeatedly over the last six weeks, what do you think light is?
And is there a difference between the full sunlight spectrum and isolated artificial
light wavelengths?
And who is going to ask the question?
(28:11):
What does this look like?
What is happening here when sunlight hits skin and through the eyes of the pregnant mother
versus the artificial light?
And what is the environment of the mother now from 1930s from the mothers of the canner
(28:34):
kids all the way to 2025?
And what does the rates of autism looks like after we have switched our environment?
Why do people overlook this?
Why do they make it so complicated?
When nothing I've said we've covered today is complicated.
(28:58):
Cells proliferate and they differentiate and they migrate and cells are developed and the
mitochondria are environmental signals.
They need two things, oxygen and electrons.
(29:21):
How does that look like now in an indoor modern world?
What does that look like for the living organism?
And especially in a time where it's so sensitive and the central nervous system, the peripheral
nervous system and the enteric nervous system are being developed.
(29:47):
And show me one autistic example where the autistic does not have additional comorbid
problems with the peripheral nervous system or the enteric nervous system.
I will beg to offer, I suggest that every autistic person has an implication to the central
(30:14):
nervous system which is the easy one.
It's autism at its core is a problem at the central nervous system but show me one autistic
that doesn't have a problem with the central nervous system, the enteric nervous system
and the peripheral nervous system all three in one.
(30:35):
So let's look at the neuroepithelial studies.
This timeline here for the circadian biology there are animal studies that back this, this
prenatal light shifts alter brain development in animal studies.
In human data it's not so direct.
(30:57):
We won't go here but we know from studies from UC San Diego and the studies with the
machine learning from Dr. Ben Ari that came on, autism is in the womb.
It's not difficult here to predict autism in the womb anymore.
(31:22):
Downstream of this with the development of the autistic, maybe the child or young adult
even.
There are so many problems with migration.
The data are so impressive here.
Maybe there's a hyper connection and maybe some areas are hypo connected.
When do you think this occurs?
(31:44):
In neuralation and remember the domino example, neuroepithelial cells, this is the foundation.
This is where differentiation and migration is off.
Everything, the whole blueprint of the developing living organism with the central nervous system
(32:06):
and the enteric and peripheral nervous systems are going to be off.
With autism there are many mismatches.
There are many areas of the brain or the peripheral problems with motor control and the GI problems
in the enteric nervous system.
(32:29):
There are so many problems here.
With autism the hyper and hypo connections.
Let's talk about this with the over differentiation, the problems with differentiation here during
this timeline.
The neuroepithelial cells in the neural tube, the dorsal region of the neural tube, this
(32:50):
is the future cortex for the living organism.
This is very deep but this differentiation and these neurons are implicated here around
week six.
The cortical plate has extra neurons and spots.
(33:10):
For the temporal lobe this is vast for autism.
The over differentiation will have overpopulated local circuits forming dense, hyper connected
networks and childhood.
What this looks like for the autistic phenotype is this.
(33:33):
Hypersensitivity to sounds is what this means.
Remember the episodes on sensory processing.
Right here is when this is developed.
So hypo connections from the migration, failure.
So when the neural tube closes at around day 26, there is stress from the neuroepithelial
(33:58):
cells and they produce too few radio glia and it's misaligned.
Hypersmith for the frontal cortex gets stuck in deeper layers and migrate to wrong spots.
By month three, the prefrontal cortex lacks proper connections.
(34:22):
In addition, the parietal cortex where sensory integration occurs and the cortex here in
the parietal kind of orchestrate downstream behaviors based off of this.
And autistic children, autistic phenotypes of all ages, they lack the social ability.
(34:46):
They miss the social cues.
So what happens with the neuroepithelial cells in the ventral tube?
And this is where I want to stop because the ventral tube will eventually make the brain
stem, the mesencephalon.
And this problem here with the autistic phenotype and the developing embryogenesis because
(35:13):
folate is here.
I don't want to talk about folate too much next time, but for now since we've mentioned
folate, this shortage of neuron output will occur and these dorsal cells, this over-proliferation
implication, this brain stem area, this automatic area that the living organism uses to bias
(35:40):
our attention.
Remember the very first thing that Donald Triplett's father, the first child in the
Canner paper.
Donald Triplett, his father wrote over 30 pages documenting Donald's abnormal kind of
social withdrawn behavior.
(36:00):
And the first thing that Donald Triplett said, and I'm reading this directly from the Canter
paper right now, he seems to be self-satisfied.
He has no apparent affection when petted.
He does not.
Observe the fact that anyone comes or goes and never seems glad to see father or mother
(36:27):
or any playmate.
He seems almost to draw into his shell and live within himself.
Remember one of my biggest takeaways here with the whole podcast to explain the autistic
phenotype.
(36:49):
The biology that gives us autism allows us to be comfortable within ourselves.
It is no question.
It is undisputed.
It's not even a debate.
You can't even debate it that the autistic phenotype enjoys being within themselves.
(37:10):
These dreamlike states, the outside world is uninteresting.
Why I say that is, the biology creates us to be more alone, withdrawn from society.
Withdraw from the environment.
(37:30):
And I'm telling you, this is occurring from this early embryogenesis period.
Something is causing us to be abnormal.
And a large part is the migration problems.
What is causing the migration problems during embryogenesis and all the way through the
(37:52):
womb as the central nervous system is being developed.
If you are listening to the podcast, listening to the episode, please feel free to leave
a review or rating.
In podcasting, reviews, ratings and downloads are huge.
In Apple Podcasts, we have five stars.
(38:15):
Nothing but five stars, so I very much appreciate that.
Please feel free to leave more.
I would love your feedback.
You can contact me on x at rps47586.
We can have conversations about autism.
I'm always open and willing to have conversations about autism.
(38:37):
I am telling you, autism is the love of my life.
But remember what we just covered and how that should be easier to understand for you.
You can check out the YouTube page for all the full length videos and shorts and clips.
You can check out the Hoplink for links to all of the podcasts across different platforms.
(39:01):
You can email me info.fromthespectrum.com.
And thank you for listening to From the Spectrum Podcast.
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