Autism is a Disease of Abnormal Microglial Activation - Part 3April 23, 2023
Autism is a Disease of Microglia Activation that Damage Nerve Fibers - Part 3
Ok, last week we learned the incontrovertible proven fact that kids with autism have mitochondria that are being overwhelmed and are unable to handle the volume of electrons they are being presented. Some escape and make reactive oxygen species that cascade down to the hydroxyl ion. All the salvage steps in between; superoxide dismutase, catalase, and glutathione, get overwhelmed, as can be proven by lab tests showing dramatic alterations in autistic kids' blood.
All of those natural "anti-oxidants" are not sufficient to protect against the making of the hydroxyl ion (OH-). The hydroxy ion attacks the double bonds in the plasmalogen molecules and makes malondialdehyde, which is elevated in autistic kids as well. Now we have damaged membranes in the axons of our nerve cells. That malondialdehyde is a potent stimulator of microglia. Microglia are the garbage trucks of your brain, your macrophages, tasked with fighting invading germs, cleaning up unused synapses, dead cells, and damaged axons.
Wups! Cleaning up damaged axons? Yes. They are just doing what microglia are meant to do. When they see a damaged axon, that speaks to a diseased cell that needs to be tidied up and cleaned out before it sets off more inflammation that damages other cells. In autism the microglia just got sucker-punched by an internal problem of too many electrons and inadvertently started attacking the wrong thing.
Malondialdehyde is elevated in autistic kids' siblings too, just not as much as in the affected child. That is what argues for some genetic susceptibility in autism, or common environmental exposure. The microglia kill the cells they attack by flooding them with excess glutamate. At the same time, astrocytes in the brain frantically try to suck up the extra glutamate to calm the fire down. All of those phenomenon have been proven in lab tests.
An epic struggle ensues. Younger children have much less myelin in their brains, giving them a much smaller reservoir of reserve to battle oxidizing events, followed by microglial attack. (This is why autism starts in early childhood when the least bit of extra inflammation sets it off.). In the experimental model of autism induced by the chemical cuprizone, you can identify that females get much less demyelination in their brains to the same dose of cuprizone, accounting for the 3:1 ratio of autism in boys to girls. And yes, in the animal model of cuprizone-induced mouse autism, the tiny bit of estrogen that female baby mice have over baby male mice is sufficient to protect the females. What levels do human boys have compared to girls? Human girls, 0.6 pg and boys 0.08. Human adult women have 100-175 pg.) And estradiol is especially protective against glutamate toxicity.
Aha! It's glutamate secretion by microglia that kills off the neuron. It gums up and stops the methyltransferase system (B12, folate, homocysteine) and makes homocysteine jump. The cell starves to death and dies. Kids with autism have horrible methylation problems and need a ton of supportive supplements to get over the hump and fix the defect. More B12, folate, Betaine, B6, choline, creatine, and finally.....the kid's brain can calm itself down and get back to normal behavior.
Take-home summary. Autism is the endless cycle of microglia activation set off by overwhelmed redox systems. Microglia activate and attack the damaged, plasmalogen-deficient axon, thereby activating more microglia. Round and round, never escaping. The overwhelmed brain needs extra plasmalogens to rebuild and protect the nerve fibers, methylation support, and extra mitochondrial support to put out the fires....and that is all possible.
Guess what happens when you give plasmalogen precursors to make more myelin? Just guess. Yup! The Lone Ranger comes riding over the hill. You can almost instantly (within weeks) turn off demyelination in every mouse and animal model ever studied. This turns out to be the key. More plasmalogen building blocks. Pulls the rug out on all the extra stress and vicious cycles the brain is in.
That is Goodenowe's genius. He designed and is now making the plasmalogen precursor to make more myelin. It turns off microglial activation just like that. It's called Prodrome Glia. In effect, it provides sufficient building blocks for the brain to repair itself and break the neverending cycle of reinforcing microglia activation and demyelination.
www.What will Work for me. I am all in. Goodenow is launching his nationwide Autism study with his collaborating doctors, of which I am one. We are just waiting the details of how to sign people up. And all the "drugs" we sure are actually just supplements. GRAS. Generally recognized as safe. We just haven't had the Prodrome Glia until now. Now we do.
And it's not just autism. This mechanism is probably also what ADHD is actually all about, but with a slightly more mature brain that has just enough materialto stay a little bit ahead. Many are beginning to argue they are just different parts of the same spectrum. Got that? ADHD too....
References: Biomarker Insights, Annual Review of Immun, Neurosci., MDPI, Neurobio of Disease, Jr Clin Investigation, J Neurosci, J Immunology, PLOS One, Molecular Autism, Spectrum News,
1. Ok, keep it simple. What happens when you get too much hydroxyl ion? Answer: You damage plasmalogens in the myelin sheath around nerve axons and you make malondialdehyde and lose plasmalogens.
2. Autistic kids have more or less malondialdehyde? Answer: Way more (meaning dramatic loss of total plasmalogen pool)
3. Malondialdehyde is a potent trigger for what? Answer: Microglia (brain's garbage trucks) activation. You turn on the garbage trucks that come and attack the damaged membranes, stripping off the myelin and killing the cell with flooding glutamate.
4. Glutamate does what? Answer: Too much of it and you shut down the methylation cycle, and you starve the cell to death.
5. Can I fix that? Answer: Yes. You can give the plasmalogen building blocks to rebuild myelin and methylation vitamins and building blocks to give all the extra nutrition the autistic kid needs.
6. Wait, wait, wait.....I have more questions. Is ADHD and Autism part of the same spectrum? Answer. YES. and Prodrome Glia will probably help both syndromes in a similar fashion. Maybe even faster for ADHD as it is a milder form.
7. Wait, wait...... Answers: next week. (See why I argue that Goodenowe is going to get a Nobel Prize in Medicine? This is a major emerging story.)