How does adenosine accumulate in brain and cause sleep?

Submitted by Lojcs t3_11asek4 in askscience

The answer of this question says the glycogen in brain is eventually depleted over time which causes an atp shortage and abundance of adenosine, which causes sleep; and in sleep the cells can restore their glycogen reserves and break down the built up adenosine to wake up.

Im a bit unsatisfied with this answer. How does brain run out of glycogen? Do neurons use more energy than what can be supplied to them? And how do they produce atp once you wake up if the breaking down of adenosine into inosine is what makes you wake up in the first place?

If anyone has further knowledge on the original question I'd be glad to hear it too.

Thanks

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CharlesOSmith t1_j9ud7ak wrote

This is a pretty dense review, but it covers your topic extensively. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4544655/

To briefly state one point they examine; the changes in glycogen levels observed in the sleep/wake transition, may be more diagnostic of that transition happening, and not actually a causative agent of that transition.

Similarly two other reviews examining the role of adenosine in sleep found that while adenosine does have a role in sleep, it is much more specific in its function, not a master "go to sleep" signal https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2769007/, and that the role adenosine takes changes depending on where in the brain, and what receptors it is working on https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6650574/

Looking around for publications, its clear that there is a lot of work being done and different camps with different models they are testing. I don't think their is a complete mechanism that everyone agrees on.

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Ebayednoob t1_j9uidgi wrote

I'm super curious as well, I've been digging into glutamate inhibition on neuronal NMDA receptors and found this while looking into cerebral spinal fluid flushes during REM sleep.

https://academic.oup.com/sleep/article/37/12/1919/2416791

"These results demonstrate that sleep deprivation and subsequent recovery-induced changes in high-energy phosphates primarily occur in gray matter, and increases in phosphocreatine after recovery sleep may be related to sleep homeostasis."

It's not an answer, in fact it just brings more questions. Human sleep and the brain is a tough puzzle.

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greenappletree t1_j9x5fc7 wrote

it causes sleep because when adenosine binds to specific receptors in the brain, it slows down the activity of neurons, reducing arousal and promoting sleepiness. adenosine can also increase the release of sleep-promoting neurotransmitters, such as GABA, which further enhance the feeling of drowsines

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AdEnvironmental8339 t1_j9xuy6h wrote

How does the adenosine slow down the neurons activities ?

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greenappletree t1_j9z23l9 wrote

so in the brain we have two main type of neurons ( excitatory and inhibitory ) or glumate vs gaba. When glumate is release it causes a neuron to fire and thus exitatory. Adenosine is release when neurons fire sometimes (what we call presynaptic) and feed back onto itself, when it binds to the receptor it inhibit glutamate release and thus decreases activity. There are other mechnism, like I mentioned above such as increasing release of gaba, but I think this is the main one.

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