Microglial tunneling nanotubes

[Wishful]

https://www.sciencedaily.com/releases/2024/07/240726113357.htm

"A recent study highlights that microglia establish connections with neurons through tunneling nanotubes. The researchers observed that microglia utilize these tubes to facilitate the clearance of toxic proteins from neurons and to promote neuronal health."

In addition to removing toxic proteins, these nanotubes also transport healthy mitochondria into neurons. It seems at least possible that these nanotubes might play a role in ME, and something researchers haven't looked for yet, since they didn't know they existed. SciendDaily also had a story about how the density of GABA receptors on certain neurons strongly affected circadian rhythm. The more they look at the brain (and the rest of the body), the more complexity they find. These discoveries and the new tools that lead to them are encouraging, but the potential for still-hidden complexity that could be the root cause of ME is much less encouraging.

 

[Wishful]

I've thought of a possible model for ME, based on these nanotubes. Microglia are a good candidate for playing a major role in ME, connecting immune system abnormalities with neurological symptoms. When a glial cell connects to a neuron with a nanotube, it transfer proteins and mitochondria. That makes it likely that other material is transferred: signalling molecules, building blocks, waste molecules, held in vesicles or floating free. ME might alter the contents of microglia, and thus what gets transferred to neurons. Immune activation in the body makes that worse, so PEM might be the result of more of <whatever> being transferred into neurons, hampering their function, resulting in symptoms. If this nanotube activity depends on neural activity, that could explain why cognitive exertion results in the same PEM symptoms, but with a shorter delay.

Now that these nanotubes have been discovered, models such as this can be tested. Does nanotube activity depend on neural activity? Measuring what gets transferred might be tricky, since these nanotubes are tiny and probably short-lived (maybe microseconds?).