Unlocking the secrets of myelin repair
neuroscience.stanford.edu
neuroscience.stanford.edu
It seems like we should transplant more than organs.
See: https://www.bbc.co.uk/bbcthree/article/347828f8-6e7f-4a9b-92...
https://www.economist.com/technology-quarterly/2023/09/25/wh...
> In 2020 Irina Conboy of the University of California, Berkeley, and her colleagues found that replacing half of an old mouse's blood with just albumin, a blood protein, and saline solution had the same rejuvenating effect as young-mouse blood. Old blood may need filtering and dilution, not supplementing.
https://news.berkeley.edu/2020/06/15/diluting-blood-plasma-r...
[0] https://www.biorxiv.org/content/10.1101/2022.09.21.508765v1....
Unless if you're on Ozempic until you literally dry out every single fat reserve in your body and your brain has to resort to breaking down the myelin sheaths (something that can happen in ultra long distance running, hence why hallucinations sometimes happen on 100+ mile runes), then the GLP1-RAs wouldn't be able to force the body to break down the fat in the brain.
To the best of my knowledge, GLP-1's have 0 direct impact on brain fat metabolism or myelin sheath breakdown.
Side note, GLP1 based therapies are being investigated for improving brain health and potentially helping prevent the development of neurodegenerative illnesses, potentially because of an anti inflammatory feedback mechanism it activates when its able to reach tissues outside the gut. (natural GLP1 is usually broken down ~5 min in the body after release)
I've never heard of this before today, but if it's true then that's terrifying.
Just to zoom in on this -- the understanding of how GLP1 based therapies work seems to also be evolving to have the benefits primarily be brain-focused. While of course GLP1 interacts in lots of ways with your other organs, but the effects on appetite suppression (and suppression of other urges) seems to be majorly brain based.
Some research into how it might work together:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9455625
In fact I wonder if the negative effects of GLP1 drugs (gastroparesis, GI issues) might be completely gone if we can target the agonists towards the brain only somehow.
When your pancreas releases glucagon, adipose tissue (compromised mostly of adipocytes - "fat cells") respond with lipolysis, converting their stores of triglyceride ("stored fat") into glycerol and free fatty acids, releasing this into the bloodstream. Various tissues use the free fatty acids directly, while others (like the brain) rely on gluconeogenesis to create a source of glucose.
Tissues that store glycogen (muscles and liver primarily) also respond by breaking this down into glucose, but this has quite low energy density of hydrated glycogen compared to fatty tissues, and an adult only stores in the ballpark of half a kilogram. This is sometimes referred to as "water weight".
Another response is proteolysis in the muscles, where muscle proteins are broken down ("muscle wasting") in order to feed energy demands.
Point being, the body does not randomly look for fatty acids in the body to tear down - the process of weight loss is a strictly controlled and centrally coordinated mechanism to maintain a steady energy level in your bloodstream. Your cell membranes are also made of fatty acids so all hell would break lose long before it got to myelin if it just started randomly picking things apart!
When in a high-glucagon and low-insulin state (that is, there is a demand for more fuel in the bloodstream than is present), after the liver has used up its glycogen stores for fast and easy glucose production, liver cells redirect most or all of its oxaloacetate supply to the process of gluconeogenesis to produce more glucose for the bloodstream from free fatty acids and glycerol released from fat tissue, as well as some other non-carbohydrate sources.
In this state, the liver's own cells lack the key incredient to finish metabolism of free fatty acids, where acetyl-CoA is combined with oxaloacetate to form citric acid for the Kreebs/citric acid cycle. Instead, the cells start converting acetyl-CoA into ketone bodies and releasing these into the bloodstream to further increase fuel availability.
Cells with mitochondria can metabolize various things including free fatty acids directly, but free fatty acids cannot pass the blood-brain barrier. Ketone bodies can, and while they have to be converted back into acetyl-CoA to be used, the liver does this to keep the central nervous system alive in a situation where glucose production might not cut it.
You only have high levels of ketone in your body after long periods of fasting/starvation (e.g., 24 hours or more), prolonged exercise or if on a diet that forces the pathway with insufficient carbohydrate.
This is because one of the ketone bodies is acetone, a result of spontaneous breakdown of one of the other ketone bodies. Only the liver can break down the acetone, and as it floats around the blood some of it ends up exhaled.
(At very high levels of ketone bodies you end up in something called ketoacidosis. In this state your blood turns acidic, which can quickly develop into a medical emergency. This mainly happens to those with health issues like type 1 diabetes.)
I found this interesting when I heard it...
But MS presents in females vs males at 3:1 according to the MS society.
Whats interesting is this article from NIH
>"Androgens show sex-dependent differences in myelination in immune and non-immune murine models of CNS demyelination" [0]
it discusses the enzyme-like activities of nanomaterials, specifically how the iron cores of biogenic ferritins act as natural nanozymes to scavenge superoxide radicals
The first sentence is pretty unpackable to some interesting "huh." moments:
Neuroprotective, anti-inflammatory, and remyelinating properties of androgens are well-characterized in demyelinated male mice and men suffering from multiple sclerosis. However, androgen effects mediated by the androgen receptor (AR), have been only poorly studied in females who make low androgen levels
But the Stanford study identified SRF (serum response factor) as a pivotal regulator of the genes involved in the cellular structure of oligodendrocytes—the glial cells responsible for myelinating nerve fibers in the brain and spinal cord.
The Nature study goes on about nanozymes and how they may be able to affect remelination. [1]
This NIH study discusses the gender differences of presenting MS in male/female rats as it pertains to where MS markers are found, whereas in females its found in spinal, but in males in the cerebellum...
So if the growth of myelin is different in females than males, the markers occur in a gender dependent manner, and MS presents 3:1 females - its the myelination's development order thats calling out for observation...
I looked up the etymology of myelin - and intersingly:
>’: The ‘my’ in ‘myelin’ comes from the Greek word ‘myelos’ which means ‘marrow’ or 'the innermost part’. So, ‘myelin’ refers to the soft material found in nerve tissues."
So as it was mentioned that females develop from the outside in, and myelin is the innermost soft tissue in the nerve, and MS present in females 3:1 - is this just all coincidence or is it just me?
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Anecdote. when my daughter was a toddler, we kept catching her getting into the fridge and eating gobs of butter.
I called my grandmother a life-long surgical nurse to ask if this was odd. She said "Heck no! Let her do it. Her brain is telling her she needs fats for development. Its good for her brain" - Shes wicked smart now. (but Ill take credit for the genes :-)