More on Sleep, ATP, and Adenosine
We spend roughly 1/3 of our lives in the state of sleep. Researchers are beginning to learn why we must do this, and are gleaning hints of possible technologies for bypassing at least part of the sleep imperative, and doing well on less sleep.
“For a long time, researchers have known that sleep deprivation results in increased levels of adenosine in the brain, and has this effect from fruit flies to mice to humans.” Abel said. “There is accumulating evidence that this adenosine is really the source of a number of the deficits and impact of sleep deprivation, including memory loss and attention deficits. One thing that underscores that evidence is that caffeine is a drug that blocks the effects of adenosine, so we sometimes refer to this as ‘the Starbucks experiment.’”
Abel’s research actually involved two parallel experiments on sleep-deprived mice, designed to test adenosine’s involvement in memory impairment in different ways.
One experiment involved genetically engineered mice. These mice were missing a gene involved in the production of glial transmitters, chemicals signals that originate from glia, the brain cells that support the function of neurons. Without these gliatransmitters, the engineered mice could not produce the adenosine the researchers believed might cause the cognitive effects associated sleep deprivation.
The other experiment involved a pharmacological approach. The researchers grafted a pump into the brains of mice that hadn’t been genetically engineered; the pump delivered a drug that blocked a particular adenosine receptor in the hippocampus. If the receptor was indeed involved in memory impairment, sleep-deprived mice would behave as if the additional adenosine in their brains was not there.
...To see whether these mice showed the effects of sleep deprivation, the researchers used an object recognition test. On the first day, mice were placed in a box with two objects and were allowed to explore them while being videotaped. That night, the researchers woke some of the mice halfway through their normal 12-hour sleep schedule.
On the second day, the mice were placed back in the box, where one of the two objects had been moved, and were once again videotaped as they explored to see how they reacted to the change.
“Mice would normally explore that moved object more than other objects, but, with sleep deprivation, they don’t,” Abel said. “They literally don’t know where things are around them.”
Both sets of treated mice explored the moved object as if they had received a full night’s sleep.
“These mice don’t realize they’re sleep-deprived,” Abel said.
Abel and his colleagues also examined the hippocampi of the mice, using electrical current to measure their synaptic plasticity, or how strong and resilient their memory-forming synapses were. The pharmacologically and genetically protected mice showed greater synaptic plasticity after being sleep deprived than the untreated group.
Combined, the two experiments cover both halves of the chemical pathway involved in sleep deprivation. The genetic engineering experiment shows where the adenosine comes from: glia’s release of adenosine triphosphate, or ATP, the chemical by which cells transfer energy to one another. And the pharmacological experiment shows where the adenosine goes: the A1 receptor in the hippocampus. _MedicalXpress
Abel's is a sophisticated experiment which covers a lot of possiblities. Combining the findings of this experiment with findings of previous experiments gives one a fuller picture of what is going on.
The brain has evolved certain activity in N2 sleep (sleep spindles) which apparently promotes the production of ATP from adenosine and phosphate groups. As ATP levels rise in N2 sleep, adenosine levels drop. So the sound sleeper receives both the benefits of higher ATP energy levels and the improved learning that results from lower hippocampal free adenosine levels.
More on sleep spindles (PDF)
Adenosine is a potent pharmacological agent, powerfully affecting heart rhythms. It also affects central nervous system activity in a largely inhibitory function, and also exhibits anti-inflammatory effects.
Adenosine and deep brain stimulation (DBS)
Why Do We Sleep? A brief look at stages of sleep, and possible benefits of sleep.
Cross posted to Al Fin, the Next Level
How could we manage on less sleep? The fastest route to achieving high-functioning sleep reduction would seem to involve electromagnetic brain stimulation or inhibition over particular brain areas at specific pulse frequencies. The aim would be to reduce adenosine levels -- and increase ATP levels -- in specific areas of the brain including the hippocampus.
Pharmacological methods for blocking adenosine's effect, such as used in the experimental mice in the study above, offer another possiblity -- although a time delay before approval for a new drug of at least 10 years is to be expected.
Genetic techniques for modifying adenosine production or re-uptake and ATP synthesis, are another likely approach -- eventually. At the present time, genetic (and epigenetic) treatment methods are far too primitive and clumsy to risk for such an objective as sleep reduction, for most people.
Other neuromolecules are likely involved in this puzzle, but at least this information offers a place to start.
Labels: brain rejuvenation