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Sophist
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21 Oct 2013, 9:20 am

A little known fact: what makes bald mice bald and auties autistic may have more in common than ya think. 8)

http://scienceoveracuppa.com/2013/10/20 ... in-common/


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Fnord
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21 Oct 2013, 9:56 am

I do not recall ever having been bitten by a bald mouse.


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Callista
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21 Oct 2013, 10:38 am

Is it like Spiderman? Get bitten by a bald mouse, and you get autism powers!! :lol:

Srsly though, I don't get why bald mice specifically have any real similarity to autism. The idea that our stem cells stay too young, too long, is interesting, but... I'm not sure. I guess I'll have to look into it. I don't think it's specific to autism. There's probably more to it than that--maybe it's some mechanism that changes the way the autistic brain develops, but it could also be a symptom of a more fundamental difference.

Yeah, this is going to be one of those things I have to research.


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Joe90
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21 Oct 2013, 11:38 am

I need to get bitten by something that gives me NT powers.


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cavernio
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21 Oct 2013, 11:48 am

Interesting.


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Fnord
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21 Oct 2013, 11:53 am

Aspieman!
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Does whatever
An Aspie Can!

:lol:


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Sophist
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21 Oct 2013, 12:03 pm

Fnord wrote:
I do not recall ever having been bitten by a bald mouse.


You were probably just too young to remember. :P

Callista wrote:
Srsly though, I don't get why bald mice specifically have any real similarity to autism. The idea that our stem cells stay too young, too long, is interesting, but... I'm not sure. I guess I'll have to look into it. I don't think it's specific to autism. There's probably more to it than that--maybe it's some mechanism that changes the way the autistic brain develops, but it could also be a symptom of a more fundamental difference.


This kind of overgrowth/undergrowth does change the way the brain develops. Another interesting thing is that when the "timing" is off, this affects the migration of inhibitory interneurons into the neocortex as well. Ultimately, this can cause hyperexcitation of the cortex, which is closely linked with the cognition we typically think of as "autistic". Treatments like low-frequency repetitive transcranial magnetic stimulation (rTMS) specifically ramp up those inhibitory cells present (especially double bouquet GABAergic cells), decreasing local excitation and calming some of the symptoms. This specifically only occurs with low-freq rTMS though, not high-freq.

The thing about the bald mice is that, even though we're talking different tissue types, the processes are very similar. If you prolong progenitor proliferation in mice, you can risk overgrowth of tissue, undergrowth if the effect is more severe, or even tumor development at its most severe form. Autism is very similar, but we're talking brain, not hair. If Variable A targets the developing brain (be it a gene, some other endogenous effector, or some exogenous insult), it can create an overgrowth of mature cells, in this case an increase in the number of cortical minicolumns, or if ramped up a bit more, it can prevent tissue maturation in focal areas (called "dysplasias"), and if ramped up REALLY high like in Tuberous Sclerosis, it can cause tumors.

Different tissues, basically the same process. And, it may not have been clear in the blog, but the vast majority (and by "vast" I mean 90% +) of autistics, including "high-functioning" auties, show signs of unusual cortical growth, including increased minicolumnar numbers (postmortem), greater gyral complexity and diminished corpus callosum size (MRI), and dysplasias (underdeveloped tissue) and heterotopias (misplaced tissue) (postmortem). Each of these traits are the direct result of targeting the progenitors producing neurons for the cortex.

Does that make some sense?


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Callista
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22 Oct 2013, 12:16 pm

Yep, it does. It seems to me that something like that would cause more than just autism, though. Depending on how you were affected and where your brain had been most changed, you could end up with just about any neurodevelopmental issue.


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22 Oct 2013, 12:44 pm

Why exactly should I trust someone named Sophist? :P Anyway, interesting find, but I'm with Callista here.


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Sophist
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23 Oct 2013, 2:56 pm

Callista wrote:
Yep, it does. It seems to me that something like that would cause more than just autism, though. Depending on how you were affected and where your brain had been most changed, you could end up with just about any neurodevelopmental issue.


To some extent, yes. Autism isn't just a particular brain area or network of areas "not working". Not that that isn't also part of it, but it can also lead to abilities as well. (That would be a whole further discussion on how ability and disability can have more in common than "average".)

But autism does include many "smaller" issues too. It's rife with various learning disabilities (in the US definition of the word). Most auties would also fall somewhere along the ADHD spectrum. Many of us could have a co-occurring dx of OCD too.

So truthfully, even though the tone of your post argues doubt, your point could make quite the opposite. Autism IS the entire brain. And, yes, there's many sub-conditions that can be included under that heading. ADHD, OCD, LDs, etc., all depending on what system has been more affected, which varies by person.

This Sunday on the blog I'm planning on writing about the evidence showing that autism has embryological origins (i.e., the first 8 weeks of life) and that it's targeted to the progenitors supplying the brain, especially the cortex. What is shocking is that evidence of prolonged proliferation of the cortical progenitor pool is present in 90%+ of autistics. Back when, even though there was good evidence that a significant portion of auties displayed increases in minicolumnar numbers, I still wasn't convinced this was at the root of the conditions. But my fiance's more recent work of the past 2-4 years has convinced me. And the thing that did it? Though the paper isn't published yet, his team was able to blindly dx almost 100% of cases of autism through a combination of three characteristics indicative of altered progenitor proliferation: reduced gyral window depth (the gyral window is the empty space contained within a gyrus so that it looks kind of like an upsidedown "U"), gyral complexity (a smooth-surface mouse brain is very uncomplicated, a human brain considerably moreso, and auties have even MORE complicated gyral patterns), and reduced corpus callosum size. Also, in two separate studies of postmortem work, even though the numbers weren't huge (about 10 brains per study), the vast majority of the tissues show dysplasias (underdeveloped sections of cortex) and heterotopias (misplaced cells). Below is a picture of a heterotopia in an autistic person, located in the germinal zone surrounding one of the ventricles:

http://corticalchauvinism.files.wordpre ... topias.jpg

The cells have formed "nuclear" formations, which are kind of a hodge podge mix of cells together in a little ball, as opposed to "cortex" that forms straight rows. They also stain differently, giving an indication that they are not the same cell type as the surrounding normal tissue. Iirc, from the study that particular image came from, 7 out of 9 cases showed evidence similar to this.

The only way you get these effects is by targeting the proliferation of cells, which happens very early. You don't get this postnatally unless there's some sort of tumorous process going on in which proliferation hasn't shut off.

Ganondox wrote:
Why exactly should I trust someone named Sophist?


True... I do often regret my choice of nick for its more popular meaning. But I've had it since 2004 so I kinda feel stuck with it. ;)


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Sophist
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27 Oct 2013, 7:23 pm

/me wonders whether this explanation might make some more sense?

http://scienceoveracuppa.com/2013/10/27 ... of-autism/

A little less about bald mice, a little more about autism. ;)


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