Brain’s ‘wiring insulation’ is one of the major factors of age-related brain det

[morganism]

“A key feature of the ageing brain is the progressive loss of white matter and myelin, but the reasons behind these processes are largely unknown. The brain cells that produce myelin - called oligodendrocytes – need to be replaced throughout life by stem cells called oligodendrocyte precursors. If this fails, then there is a loss of myelin and white matter, resulting in devastating effects on brain function and cognitive decline. An exciting new finding of our study is that we have uncovered one of the reasons that this process is slowed down in the ageing brain.”

“We identified GPR17, the gene associated to these specific precursors, as the most affected gene in the ageing brain and that the loss of GPR17 is associated to a reduced ability of these precursors to actively work to replace the lost myelin.”

The work is still very much ongoing and has paved the way for new studies on how to induce the ‘rejuvenation’ of oligodendrocyte precursor cells to efficiently replenish lost white matter.


https://www.port.ac.uk/news-events-and-blogs/news/brains-wiring-insulation-is-one-of-the-major-factors-of-age-related-brain-deterioration

Functional genomic analyses highlight a shift in Gpr17‐regulated cellular processes in oligodendrocyte progenitor cells and underlying myelin dysregulation in the aged mouse cerebrum

https://onlinelibrary.wiley.com/doi/10.1111/acel.13335

[morganism]

Gut Molecule Linked to Decreased Myelination in Mouse Brains

How it’s doing it, we still need to understand.”

Mazmanian and his colleagues engineered two strains of bacteria to produce enzymes that convert the amino acid tyrosine to 4EP in large amounts. Germ-free mice—which lack a gut microbiome—fed these bioengineered bacteria had high blood levels of 4EPS and altered behaviors. Compared with control mice, which were fed bacteria without the engineered enzymes, they showed increased anxiety-like behaviors, atypical social behaviors and fewer ultrasonic vocalizations.

Both groups of mice performed similarly on cognitive tasks, however, suggesting that the effects of increased 4EPS are limited to emotional behaviors. In line with that idea, mice with high levels of 4EPS had unusual connectivity patterns in brain regions related to emotion processing, functional ultrasound images showed.

At the cellular level, the animals have immature oligodendrocytes, brain cells that produce myelin. They also have low levels of myelination throughout the brain, which could explain the connectivity changes, the researchers say.

Treating 4EPS mice with the drug clemastine fumarate, which encourages oligodendrocytes to mature, prevented the increased anxiety behaviors in the animals, the researchers found.

“What that tells us is that the arrest in oligodendrocyte maturation is critical for the changes in behavior,” Mazmanian says.

company that Mazmanian co-founded and directs, is conducting a clinical trial of an experimental drug, AB-2004, that could sop up 4EP throughout the gastrointestinal tract, with the goal of treating irritability in autistic children. Giving AB-2004 to mice with high levels of 4EPS lowers those levels and lessens the animals’ anxiety-like behaviors, the team found in a study in Nature Medicine, also published today.

The drug was safe and well-tolerated in 26 autistic adolescents, the new study shows, and preliminary evidence suggests that it lowered 4EPS levels and lessened anxiety and irritability in the participants. But because the trial was designed only to assess safety, it had no control group. It was also open-label, meaning that participants and their caregivers knew they were receiving the drug, increasing the chances of a placebo effect.

https://www.spectrumnews.org/news/gut-molecule-linked-to-decreased-myelination-in-mouse-brains/

[SteveMDFP]

At the cellular level, the animals have immature oligodendrocytes, brain cells that produce myelin. They also have low levels of myelination throughout the brain, which could explain the connectivity changes, the researchers say.

Treating 4EPS mice with the drug clemastine fumarate, which encourages oligodendrocytes to mature, prevented the increased anxiety behaviors in the animals, the researchers found.

“What that tells us is that the arrest in oligodendrocyte maturation is critical for the changes in behavior,” Mazmanian says.

Interesting article.  Note that clemastine is an inexpensive OTC antihistamine.  I recall recent posts on another thread that antihistamines may have beneficial effects on some symptoms of "long covid."  As I understand those empiric results, the effects for long covid are prompt, and I doubt increased myelination of neurons could be that quick.  It's also a somewhat paradoxical finding, as most antihistamines tend to be sedating.

Still, there's at least one trial that supports the idea that clemastine can promote myelination in human brains.  Multiple sclerosis is largely a demyelinating disease of the brain:

"In a small, phase II clinical trial, the oral antihistamine clemastine modestly improved the transmission of electrical signals in the optic nerve in participants with MS who had optic nerve damage. The improved transmission indicates that nerve-insulating myelin was repaired along the nerve pathways."
https://www.nationalmssociety.org/About-the-Society/News/Antihistamine-Shows-Evidence-of-Stimulating-Myelin           and:
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)32346-2/fulltext?elsca1=tlxpr

I sometimes use an antihistamine as a sleep aid.  Perhaps I'll use clemastine in particular, to maybe support this aging brain.

[morganism]

Most things i have read about myelin was about reducing "noise". Slowing random firings allows more "signal" to get thru.

I also recall a lone researcher showing that some viruses were "tunneling" thru myelin sheaths to get thru the blood/brain barrier. There is also a study positing that regular maltose could open the B/B barrier for 20 min, and was promoting it for pushing brain cancer drug infusion. If that were true, all us older folks that had malt sugar in ice cream, choc milk, etc, were leaving the barrier down, allowing whatever was in the bloodstream to flow thru....