I have to say that scientists really bother with the matter of getting us to sleep well.
No, they once again argue that when people's work and rest routines are disordered, the amyloid Aβ42 in the brain, which is closely related to Alzheimer's disease (Alzheimer's disease), cannot be cleared in time.
The massive accumulation of this protein will cause damage to neurons, further damaging the brain.
The key to regulating this change is a proteoglycan that attaches to the surface of macrophages, affecting how Aβ42 is cleaned up.
When the amount of proteoglycan adheres, the more macrophages do not work properly.
Scientists have found that under sleep conditions, the content of this proteoglycan is reduced, and Aβ42 can be cleaned up very well.
That is to say, every night you stay up, the more "dementia inducers" accumulate in your brain.
The harder you stay up late, the sooner you have dementia?
So, still boiling?
Proteoglycans are "timers"
The study can be roughly divided into two parts.
Scientists first demonstrated from the molecular mechanism level that the level of Aβ42 in the human body does change with the circadian rhythm.
Then, they found that the "timers" that controlled this change were two proteoglycans.
Let's look at the first half of the experiment.
Previous studies have found a two-way relationship between staying up late and Alzheimer's, such as many Alzheimer's patients who have had sleep disorders many years ago.
It may be that macrophages that engulf Aβ42 are regulated by circadian rhythms.
△ The macrophage sister in "Working Cell"
To demonstrate this theory, the researchers fluorescently labeled Aβ42 using the BMDM phagocytosis assay to determine whether the circadian clock would play a regulatory role.
BMDM is a macrophage extracted from the bone marrow of mice, and the experiment is designed to simulate the change of Aβ42 precipitation in a Petri dish over a 40-hour period.
The results showed that between 16-20 h after the start of the experiment, the precipitation of Aβ42 was the highest, and at about 30 h, the precipitation was the lowest.
It is not difficult to see that Aβ42 is engulfed in fluctuations with the circadian rhythm.
△Aβ42 changes (the longitudinal axis in Figure B\C is the amount of Aβ42 engulfed)
Next, the scientists conducted a detailed analysis of these macrophages.
It was found that two changes in proteoglycan content were associated with this pattern, namely heparan sulfate proteoglycan (HSPG) and chondroitin sulfate proteoglycan (CSPG, chondroitin sulfate proteoglycan).
The data showed that the content of HSPG and CSPG was higher when Aβ42 was precipitated, and conversely, the content of HSPG and CSPG was very low when Aβ42 was cleaned up in large quantities.
Through further research, the scientists discovered that this is due to the fact that proteoglycan HSPG aggregates on the surface of phagocytes as the circadian clock changes.
As can be seen from the figure below, the content of HSPG has remained high during the simulated daytime, and the amount of precipitation corresponding to Aβ42 is also very high.
After the treatment time was 12 hours (CT12) and entered the night, the HSPG content decreased, and the amount of precipitation corresponding to Aβ42 was also reduced.
Jennifer Hurley, corresponding author of the study, said it was clear that the accumulation of Aβ42 varied with circadian rhythms.
However, current research has not yet revealed why these proteoglycans affect macrophage cleanup of Aβ42.
But it still offers a new treatment idea for treating Alzheimer's:
Is it artificially increasing the frequency of circadian rhythms to enhance the cleaning of Aβ42 protein?
Brain: Ball ball you don't stay up
If you say the results of this study, it still can't stop your heart from staying up late.
Well, there are many studies below that show that staying up late is extremely costly.
Previously, a paper published in Science said that deep sleep is an important way for the brain to "clean up the garbage".
The Boston University team observed more than a dozen subjects between the ages of 23-33 and found that during sleep, human blood will flow rhythmically from the brain, and whenever there is a large amount of blood flowing out, cerebrospinal fluid will take the opportunity to enter the brain and metabolize the "garbage" deposited in the brain.
The Aβ42 protein we mentioned above is one of them.
Staying up late, on the other hand, can also affect the repair of DNA damage.
You know, if DNA damage is not repaired, it is likely to cause genetic mutations or even cancer.
A study in the Cell sub-journal Molecular Cell pointed out that DNA damage accumulated by many organisms, including humans, will be repaired at an accelerated rate during sleep.
To be able to repair these damages, our bodies even have a mechanism to call you to sleep.
……
Of course, if you insist on staying up late for a long time, you will not necessarily get Alzheimer's disease .
Because staying up late for a long time will probably not have a chance to live to old age (doge).
Address of the paper: https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1009994
Reference Links:
[1]https://news.rpi.edu/content/2022/02/10/clearance-protein-linked-alzheimer%E2%80%99s-controlled-circadian-cycle
[2]https://www.science.org/doi/pdf/10.1126/science.aaz5191