Bone marrow is linked to autism?

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Are you aware that bone marrow stem cells are a source of the brain's microglial cells? These microglia are made in the bone marrow, and then migrate into the brain. Resident microglia in the brain form an amazing 10% of the brain. This population of resident microglia cells in the brain are constantly being renewed and replaced, hence the need to make microglia all the time, in the bone marrow.

Microglia operate as the brain's immune system. Normally microglia are switched off, when there are no infections around. However, for reasons as yet unknown, sometimes these microglia get permanently switched on, and don't turn off again. There may be some fault in these microglia causing them to switch on permanently; or this may be the result of a hidden chronic infection.

This chronic activation of microglia is increasingly connected to autism, and several other neurological conditions. Chronic microglial activation causes excitotoxic damage to surrounding brain cells due to the excessive glutamate released from the microglia. These high levels of glutamate will overstimulate NMDA receptors, leading to excitotoxicity. In the amygdala, this NMDA overstimulation kicks off the anxiety and high internal mental tension felt by many autistic people.

So it is intriguing that bone marrow is the source of new microglia. These newly-made microglia are manufactured in the hematopoietic stem cells in the bone marrow.

If there were some problem in the bone marrow's hematopoietic stem cells, such that they end up producing faulty microglia, then when these microglia migrate to the brain, they may get stuck in this chronically switched on state. When you perform a bone marrow transplant, you are replacing your hematopoietic stem cells with the donor hematopoietic stem cells, so that from then on, new microglia are manufactured in "new factories", and so then the brain is being supplied with properly-working microglia.

This is not to argue for or against the idea of hematopoietic stem cell transplants. Whether the risks involved in transplant are currently too high is not the topic of this post. This post is just to show that there is a strong link from bone marrow, to the microglial cells in the brain - cells which are increasingly implicated in autism and many other brain conditions.

Last edited by Hip on 22 Dec 2010, 1:10 am, edited 1 time in total.

Where is the link?

This sounds like a hypothesis to me. Any actual evidence that this is the case?

Next headline: Air causes autism.

WiFi causes autism. Autism causes autism. Tories cause autism. Firefox causes autism. Jenga causes autism. Music causes autism. Cars cause autism.

Your mum causes autism!

society's stupidity causes autism. There is nothing wrong with us, we just decided to say screw it and not follow the herd that runs off the cliff like a bunch of lemmings.

Hmm, I am not sure I understand those responses.

Often people with Asperger's / autism have a great interest in cause and effect, one of the great qualities and virtues of this condition. How does making these remarks contribute anything interesting to the discussion?

It's an overdose of causes that are not proven, and many that have been false leads. When there is a study that actually proves something, I'm sure it will be the talk of the boards.

That being said you will probably not enjoy my first reaction, my shock at finding I have bone marrow, and autism, chalk one up for the theory.

This.

Simply put, we've stopped caring. There have been just a few too many theories (vaccines, powdered milk) and downright outlandish whatevers (apparantly we're dolphins in human bodies) for us to still be interested. No proof to anything. As the above poster said, if they found conclusive proof (and have fun with that, as it seems every scientific study just proves another one wrong), we would care.

Soft drinks cause autism.

Breathing causes cancer! Every person who has died of Cancer has had to breathe at some point.

Living causes autism.

The multiplicity of hypotheses is part of the fun, if you enjoy the detective work, the adventure, of searching for scientific answers.

If you are not interested in the processes of science, fair enough. It's not everyone's idea of fun. But many do enjoy it: examining various different speculations and hypotheses; using your own intuitions and knowledge trying to sift out the gold from the dross.

There is nothing special about autism in this respect. You find that most badly understood conditions with physical and/or mental manifestations are surrounded by lots of theories and speculations as to their cause or causes. This includes chronic fatigue syndrome, ADHD, Tourette syndrome, obsessive–compulsive disorder, Parkinson's disease, Alzheimer's disease, anxiety disorder, bipolar disorder, depression, multiple sclerosis, etc.

You need a lot of different theories: the more you have, the more likely one of them is going to hit the nail on the head.

Many of these medical/health conditions have a lot of overlap. For example, chronic fatigue syndrome and autism share several physical and mental symptoms. So answers found in one area may help explain what is going on in others.

I agree that treating autism purely as something to be cured is wrong. The asperger / autistic mindset bring something extremely valuable to humanity; something indispensable. The same can be said for obsessive–compulsive disorder, bipolar disorder, and perhaps even ADHD.

(However, perhaps people with Parkinson's disease, Alzheimer's disease and multiple sclerosis would generally feel that they would be happier without their conditions.)

Actually, there are some very smart people that hang out here and they would be VERY interested in the science. I'm willing to bet if you posted some links to a few of the studies, you would get a very different response. When you posted an hypothesis with no corroboration, you left yourself open to our skepticism. Don't give up on us, just don't spoon feed us either..

As far as I know, this kind of thing leads to Alzheimer's, not autism... Autism is not "neurodegenerative" (except for Rett's, but we know what causes that already). It's "neurodevelopmental" (i.e., a divergent developmental process that creates a different structure from the norm, rather than a process that causes damage to pre-existing structures.)

But yeah, do post the papers. If you can't post them because they're on pay sites only, just put the bibliography information (you know, journal title, issue, article, author) and I can hunt them down--my university probably has access to the article databases. There are a lot of us here who have similar access, I think.

It's an Asperger's / autism forum, so naturally there would be extremely smart people here.

Having some Asperger's myself, at one point was reasonably bright - but then I contracted chronic fatigue syndrome from a viral infection, and my brain went rapidly downhill. Anyway, that is another story.

The context of my original post was related to another thread on this site, about the reports of (very risky) bone marrow stem cell transplants having improved autism. At first glance, this seems improbable; but because I have been doing some reading on chronic microglial activation (CMA) and CMA's links to many mental conditions and neurodegenerative disorders, a plausibility argument occurred to me: that the apparent cause of the CMA believed to be linked to autism might be in the bone marrow itself, and that "rebooting" your bone marrow via transplant may lead to a marked reducing in CMA, thus improving autism.

This is not to say that bone marrow transplant is the answer, but just that the root of conditions like autism connected to CMA may be in the bone marrow. It is somewhere where further research might be focussed.

It could be something like a persistent infection of bone marrow stem cells that leads to the creation microglia that are themselves already infected, and they then carry this infection into the brain. Normally the blood-brain barrier prevents most infection reaching the brain, but an infection might sneak into the brain by riding inside migrating microglia, like a Trojan horse. This infection may remain confined to the microglial cells, but may well be responsible for their chronic activation.

If you find this general area of chronic microglial activation interesting, here are some pointers:

I just joined this forum, so I cannot post URLs just yet, but if you Google search on:

chronic microglial activation autism

you will see a number of relevant studies and articles.


Just to recap what chronic microglial activation is (as far as I understand it):

Chronic microglial activation causes damage and disruption in the brain because operating microglia pump out lots of the neurotransmitter glutamate; plus microglia may pump out quinolinic acid when they are functioning too. Both glutamate and quinolinic acid strongly stimulate the NMDA receptors on neurons. So CMA leads to chronic and permanent overestimation of NMDA receptors on neurons in the brain. This is a sort of design flaw in the brain, that microglia activation causes this knock-on effect of NMDA overestimation.

NMDA overestimation perturbs the normal balance of neurotransmitters in the brain, and in particular, within the amygdala, NMDA stimulation leads to anxiety responses. High levels of NMDA stimulation will actually burn out and kill brain cells, in a process called excitotoxicity.

You might also want to look up in Google:

excitotoxicity NMDA receptor

I hope this of interest to someone. I find it intriguing that CMA is implicated in several neurological conditions.

One interesting observation on the chronic microglial activation theory of autism / chronic fatigue syndrome, etc, is that it can offer an explanation of why certain supplements used in autism / CFS give mild improvements.

Assuming chronic microglial activation is responsible, via the NMDA overestimation mechanism, for many symptoms of autism / chronic fatigue syndrome, then by reducing this NMDA overestimation you would expect to see improvements in symptoms.

One way to reduce the NMDA overestimation is to block the NMDA receptors on the neurons with an NMDA receptor antagonist. Such an antagonist locks onto the NMDA receptor itself, and prevents this receptor from being activated by the glutamate/quinolinic acid that are unfortunately output in abundance by operating microglia.

Surprisingly, one pretty powerful NMDA blocker is magnesium. Now, it is well known that both in autism and CFS, high doses of magnesium (such as magnesium sulfate) applied transdermally as a cream over the whole body bring symptom relief from the mental tension, mental oversensitivity and anxiety states of these two conditions. I have tried this, and I know it works (to a degree). Note that most of this absorbed magnesium will leave the body after around 8 hours, so you really need to apply magnesium twice daily.

Anyway, you might well theorize that the mechanism of the anxiety relief brought by transdermally magnesium comes from the fact that magnesium blocks the NMDA receptor overstimulation. In others words, the noted improvements brought by transdermal magnesium can be construed as supporting the chronic microglial activation theory of autism / chronic fatigue syndrome.

Other (probably less potent) NMDA receptor antagonist include: zinc, progesterone, and L-taurine.

Interestingly, supplements that are known to reduce levels of microglial activation are also those that have been found mildly beneficial in autism. Supplements that reduce microglial activation include: vitamin E, and silymarin (from milk thistle herb). Again this can be construed as little bits of supporting evidence for the CMA theory.