Hi all! A happy, healthy, Hump Day to each of you and yours. All is well in my humble abode. I will be working in my normal office this fine day, which is always nice and becoming more rare in many circles these days. Today I pick up where we left off yesterday with more discussion of the brain “as a muscle”, with the implication that it can be exercised. I mean, we all have a tired brain sometimes (often these days), so that must be a tired muscle since that is the point of reference for tiredness, right? Today a quick discussion of something I brought up yesterday: How muscles play into the brain’s clearing out of junk.
As I mentioned yesterday, Intramural periarterial drainage (IPAD) of soluble metabolites is performed by smooth muscles in and around the brain to push out as waste the Beta Amyloid plaques that are thought by most to be one of two substances (with Tau tangles) causing dementia. (Here is a good link about the topic). It appears that, in the cosmic “supply and demand (assuming there is a demand/positive use) of these plaques, the problem doesn’t seem to be that we overproduce them, but instead that we remove too few of them and they build up. Think of being trapped with no toilet paper (I know…hard to imagine!!!) and being too nervous with out the Charmin to go “#2”, if you will. (“Poo poo” or “Doodie” for you who don’t use the numbering system 😉 ). In that scenario, you would get an upset stomach regardless whether you overeat or eat a normal amount. These “brain muscles”…or at least brain-oriented muscles” work with the IPAD to be one of the four ways to removing these plaques from the brain, allowing it to regenerate daily in sleep. The other three (critical) ways these plaques are removed are:
- Enzymatic/glial degradation– Using “degrading enzymes” (think Liquid Plummer) such as neprilysin, angiotensin-converting enzyme, and insulin-degrading enzyme to break down these plaques where they just dissolve away.
- Transcytosis– “promoted by inhibition of the receptor for advanced glycation end products (RAGE), which mediates transcytotic influx of circulating Aβ into brain. Successful use of the RAGE inhibitor TTP488 in Phase II testing has led to a Phase III clinical trial for AD patients” First, RAGE. Awesome work with that acronym, wordsmiths! 🙂 Mad Max would be proud. Second, transcytosis is passing one substance from one area to another without changing it into another substance. Vesicles, in cells, make this happen…so the Beta-Amyloid is passed from cell to cell until another process can get rid of it. This reminds me a little of Mike Teavee in the Willy Wonka movies. Each room is a cell and transcytosis happens using transmitting by television. (Maybe I need to open my mouth a little wider when I talk?) Perhaps the process of transferring Beta-Amyloid causes degradation just like in the movie until it is gone? The science gets hard to understand how this process removed the BA. The blood brain barrier uses this process and is amazing and challenging. It is amazing in how it prevents bad things from hitting your brain. It is challenging in that it keeps possible treatments for dementia from reaching the brain without sticking a needle into the brain itself, never a great plan compared to a shot on the arm… Using this transcytosis to our advantage is the subject of some great advances in medicine and may eventually lead to a cure! Very interesting topic…here are some links: Link Link Link
- The glymphatic system– “is a recently discovered macroscopic waste clearance system that utilizes a unique system of perivascular channels, formed by astroglial cells, to promote efficient elimination of soluble proteins and metabolites from the central nervous system.” These channels are the spaces between the cells that are being “washed” by it. This system is what most of us think of now when we think of how Beta Amyloids are removed during sleep. This is an amazing article that isn’t too far over my head: Link. Here is a very helpful, basic video on this system. Here is another really cool one. (The last discovery in this video is the IPAD. This is kind of easy to visualize. It is kind of like a systematic sponge with water running through it, cleaning the outsides of the cell walls that the membrane of the sponge is made up of. It is critically important and has a lot of promise. The muscle “kind of” pushes the fluid through these chambers in a smooth muscle (involuntary) kind of way. 🙂
Therefore…….what? Can this muscle be strengthened? It seems easy to say that it would. Improved and increased blood flow is caused by the heart beating faster during exercise. Wouldn’t that be involved in waste flow too? Simple enough…except the glymphatic system works almost exclusively when we sleep. Not much exercise in sleep mode other than running in place that I sometimes do. Therefore, exercise may help part of the yucky stuff clearance (clearing out), but it isn’t a lone ranger. Couple of links for your consideration: Link Link Link
What about brain games and mental exercise in clearing out the junk? Hmmm…not as simple…but it makes sense that it helps fight off the disease. Maybe this part is based on tomorrow’s concept: Cognitive Reserve.
Cliff Hanger!!! 😉
Mom is, by all accounts, doing ok. We are blocked from calling this week because of a big celebration they are doing. I hope the added activities and visits to the store don’t introduce COVID-19 into her center during the fun. 🙁
Here are some super cute pics from yesterday: