It’s funny how fast things can go from “I’m so understimulated I feel like I’m turning into a tree” to “Oh god oh god oh god”. Despite the stress, I’m grateful for times like these because they force critical examination of priorities and resource allocation, and usually provide a path to a more clear/pure set of both on the other side. Usually.
All that an unnecessarily cryptic way of saying “I’ve been busy, will try to keep better updated in the future.”
My reading volume around this area has gone down pretty significantly over the past few weeks, but I did tag a few interesting articles:
Glial progenitor cells of the adult human white and gray matter are contextually distinct – So this one has been rolling around in my brain a bit, and I’ve going through the “It can’t be that simple can it?” I’m actually frustrated that I hadn’t considered it despite the general theme here.
This article supports the argument that that gray and white matter astrocytes have fundamentally different functions, and they support this by showing that the genetic expression from the two groups looks very different from each other. And because RNA expression is literally function, we have a blatantly obvious set of valence physiology.
Some really interesting OF COURSE moments – they found that gray and white matter astrocyte cell volumes are roughly balanced, with region specific differences. White matter regions however had a higher cell density, reflecting their functional role in encoding external data across a larger variety of sources. Further, there are several types of WM which are functionally distinct. We’ve carried the conceit that because these cells are roughly visually similar they must be functionally similar and this evidence adds a lot more strength to the argument that this is not the case at all.
This opens the door to a kind of “network based” localization, where instead of something like “Broca’s area” we instead have astrocyte networks which may have definable network activation for similar types of behavior. For example, in order to integrate the metaphors of speech with the physical movements, we may be able to clearly define common astrocyte activation chains responsible for particular behavioral integrations.
This work (geez, am I programming javascript or something) also contributes some pretty strong evidence that oligodendrocytes are more than just passive insulators of the signalling chain, and provide active signal management. This is coherent with my recent speculation that the “purpose” of myelin is maintenance of a metabolic rather than “electrical” signal.
There’s a ton more in this work that I should discuss but the really big takeaway here is that it provides a mechanic through which valence, integrator/differentiator, “E/I”, and most other models which rely on these types of balanced dualities may function. It provides a unifying mechanic through which some phenotypes of “schizophrenia” and some phenotypes of “autism” exist as opposite ends of a single mechanic. It’s “network regionalism” provides support for both “multiple intelligences” and “multiple maturities” schemas.
Most excitingly, it’s sharpening up the research targets and kind of lighting a pretty clear path once the fUS project gets mature. This is really great work.
Developing a transwell millifluidic device for studying blood–brain barrier endothelium – From a tools perspective, something like this is something I was wondering out loud as being necessary for the next big step a few months ago.
One of the most critical issues with our current tools is that they measure one thing only, activation. Worse, nearly all of them only measure electrochemical gradient transactions rather than a much more general activation.
While this particular implementation is still pretty limited and more targeted at small molecule research rather than functional research, this type of device is exactly in the right direction. A more generalized implementation of something like this can lead to devices which measure exome leakage or other metabolic products going on in brains to give us a much more complete understanding of the environment outside of whether activation occurred or not.
Significant questions this has the potential to answer is exactly how distally programmable cells are, and whether it’s possible to induce programming effects to distal areas of the nervous system without first needing to force an astrocyte (via virus) to produce customized peptide/proteins to support it. Something like this will give us the ability to determine chemical homeostasis in brains on an individual level and provide a granular look at exactly how overlapping chemical signatures produce a particular output. This moves us from “well, something turned on and off” to actually understanding exactly what the traffic in and out of a cell looks like which underlies that “on and off”. This is a cool idea and worth following.
High-dose oral glutamine supplementation reduces elevated glutamate levels in CSF in patients with MELAS syndrome – This was interesting because it adds to the body of evidence that metabolic interactions do not necessarily depend on distinct genetic signatures to manipulate. This should be obvious as we have lots of drugs that already do this (e.g. alcohol), however work like this suggests that we should be able to target functional regions directly by phenotype.
Imagine for example a customized version of an alcohol molecule designed to deliver specific effects, and which is clearable by existing liver processes. This suggests to me that we may have a way to modify existing chemicals that are well metabolized by our nervous system to get around the expensive process of viral targeting.
Glial Glutamine Homeostasis in Health and Disease – Keeping up with the conceit, GABA/Glu appears to be the most significant metabolic “stop/go” mechanism in brains. Getting a better understanding of how this homeostasis point moves around is pretty critical to greatly improving our understanding of function, particularly with regard to degenerative/over active “conditions”.
Astrocytic Yin Yang 1 is critical for murine brain development and protection against apoptosis, oxidative stress, and inflammation – I’m still on a quixotic mission to internally arrange most of the zinc finger interactions, particularly NOTCH related ones since they are so important to inter-cellular communication. This work dovetails a bit with the “stimulation boosts methylation” hypothesis I’m currently working under.
The effect of the properties of cell nucleus and underlying substrate on the response of finite element models of astrocytes undergoing mechanical stimulations – Using FEM to model actin dynamics? Hrrrmrmmmmm.
Edit: Ooops had a few more but I guess I deleted them.