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Is it known exactly why the brain needs sleep? What's dropping low / going high when we experience mental fatigue? I can see why low glucose could result in mental fatigue, are other reasons known?

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Because the brain cell highly sensitive to glucose when its level decrease the we feel fatigue – user17552 Aug 28 '15 at 14:54
up vote 2 down vote accepted

This is not the biochemistry, but the brain regions involved are described in this article about an fMRI study:


From what I can tell, mental fatigue is attributed to low oxygenation levels. Here's a study that examines the effect of creatine in preventing mental fatigue:

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I know that these pieces of information don't directly answer your question, but they're related (and the best I could find). – dd3 Feb 10 '13 at 5:46

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