This is your brain [A1 adenosine receptor] on sleep deprivation

A1 Receptor Availability during sleep deprivation and after recovery sleep
PET scan of A1 receptor availability after 52 hours of sleep deprivation (top) compared to after 14 hours of recovery sleep (bottom). 

So I just finished my finals and moved and got a new puppy and am trying to settle into my summer lab schedule, which means I am a little late on getting this post out (but just a little late, right?). My puppy likes to wake me up early every morning with sad whining, and if not her, then the other dog finds ways to kick me in her sleep. Needless to say I am not sleeping as well as I used to, so I thought a post on sleep deprivation might be fun! I came across this article (“How the brain reacts to sleep deprivation”) a few weeks ago on social media and thought, ‘I wanna know what happens to my brain when I don’t sleep enough.’ Upon clicking on the article I realized it wasn’t just about those nights when you don’t get enough sleep, but is instead about what can happen to your adenosine a1 receptors in your brain after 52 hours of being awake (which I do not do nor do I plan on ever doing if I can help it). Still, seemed pretty cool. I kept reading.

According to the news article, researchers had some men stay awake for 52 hours straight with no caffeine while they measured cognitive abilities (specifically reaction time and memory). At the end they used positron emission tomography (PET) to look at the available adenosine A1 receptors in the brain. ‘Wait, what is adenosine?’ you may be asking. Adenosine is one of the main neural “ingredients” of feeling sleepy, and is what you block when you drink caffeine, so that’s why they focused on it for a sleep study.

Well, apparently when you deprive yourself of sleep, you end up with more available A1 receptors. This might mean that you have less adenosine binding to receptors, or maybe your brain is actually making more of the receptors themselves. What I really found interesting about this study was that people who had a larger increase in available A1 receptors did better on those cognitive tasks I mentioned earlier. Finally, the news brief states that this might help in clinical literature about depression because sleep deprivation can decrease depressive symptoms (but also once you sleep again that relief goes away). I really wanted to know more about this last point, and the only place to find more information on that is in the actual article, so that’s where I went.

I clicked on the nifty link at the bottom of the page that took me right to the original article titled, “Recovery sleep after extended wakefulness restores elevated A1 receptor availability in the human brain” (scientific journals haven’t incorporated “clickbait” into their article titles just yet). This is not an open source article, so here is my PDF copy of “Recovery sleep after extended wakefulness restores elevated A1 receptor availability in the human brain”(god please no one report me to the authorities or whoever will get mad at me for sharing this I just want science to be more available to the public).

Article Summary

What they did: Previous studies had found an increase in A1 receptor availability after sleep deprivation, so this research wanted to both replicate that as well as add another component of recovery sleep (like getting a good night’s sleep after pushing through finals week). Finally, they wanted to explore whether there might be a link between A1 receptor availability and cognitive performance during sleep deprivation.

To do this, 14 healthy male volunteers participated in the study. One week before the study participants had to keep a strict sleep-wake cycle (asleep at 11pm and awake at 7am), and four days before the study participants had to stop drinking any caffeine. This was to assure that all participants started from the same amount of sleep and that there were no confounding effects of caffeine or caffeine withdrawal. Next, they came into the lab to stay up for 52 hours straight and had a PET scan to look at A1 receptor availability. At this time they also did a bunch of cognitive tasks, such as reaction time, working memory, and also reported on general sleepiness. Finally, they slept for 14 hours and had another PET scan at the end of that to see if A1 receptor availability went back to baseline levels after a good night’s sleep. A separate group of people had their A1 receptor availability measured after a baseline 8 hours of sleep for comparison.

A1 receptor availability increase after sleep deprivation
Brain regions with significant increase in A1 receptor availability due to sleep deprivation. Error bars denote standard error of the mean (SEM). Asterisks show significant difference between sleep deprivation and recovery sleep.

What they found: The study compared the 8hr baseline group’s PET data with the experimental group’s sleep deprivation and recovery PET data using an analysis of variance (ANOVA), post-hoc t-tests, and false discovery rate (FDR) measurement of significance. They found that after sleep deprivation, A1 receptor availability increased. This was mainly seen in striatum and thalamus areas of the brain (but also in other areas). Confirming their main hypothesis, they found that a good night’s sleep (aka 14 hours following sleep deprivation) restores A1 receptor availability to that 8hr baseline level.

A1 receptor availability correlates with PVT lapses (attention/Cognitive ability), 3-back Omission (working memory), specific type of sleep during 8hr baseline, and sleepiness ratings
A1 receptor availability correlates negatively with A. PVT lapses (attention/cognition errors), B. 3-back Omission (working memory errors), C. amount of time spent in slow wave sleep during 8hr baseline, and D. sleepiness ratings

There were a lot of individual differences in how much A1 receptor availability increased, as well as how well participants did on cognitive tasks and sleepiness ratings, and these differences correlated with each other. That means that participants with a larger increase in A1 receptor availability had fewer errors and felt less sleepy. The article reports this as though there are these correlations in all the brain areas they found to have significantly increased A1 receptor availability, but the graphs (which I have included here) only show the striatum, the insula, and the temporal cortex. I had to search a little to find the supplementary material for this article, but I got to it and found that PVT lapses correlated with A1 increases in three areas (anterior cingulate cortex, orbitofrontal cortex, and striatum), 3-back omissions correlated with all those areas shown on that initial graph I showed you guys, slow wave sleep correlated with four areas (anterior cingulate cortex, insula, parietal cortex, and striatum), and sleepiness ONLY correlated with increases in the temporal cortex. But that would have made a very cluttered graph so they used the strongest relationships to showcase the correlations.

What is this link with depression? I had absolutely no idea that sleep deprivation could help with depressive symptoms. It looks like sleep deprivation can be used as a way of curbing depressive symptoms (see this review for more details) but that these symptoms come right back after a night of recovery sleep. This study thinks that adenosine must play an important role. There is actually an over-the-counter drug to combat depression that uses a precursor protein for adenosine. This, along with a few rodent studies suggesting an important role for adenosine A1 receptors in depressive symptoms, made the researchers of this study think that maybe these differences in A1 receptor availability could help tease apart some of the underlying reasons for the depressive symptoms coming back after recovery sleep. More research will be necessary for this specific interest, obviously.

Inner Skeptic

First, there were only 14 healthy men involved in this study. Not only is this just a very small sample, but this means that if women have any difference in adenosine receptors, then this is not generalizable to half the population. This is a pretty big problem that a lot of studies have, mostly because it’s expensive and time consuming to have to double your sample size and include sex or gender as a statistical factor. I would still like to see it done. You know, for science.

Next, receptor availability does not give us the full story. Are there more receptors being made (or being put into the cell membrane) or are the receptors binding adenosine less (maybe through the physical folding of the receptor protein changing)? In understanding the specific mechanisms of sleep deprivation and how that might affect mood and cognitive abilities, that seems like an important fact.

Finally, and this is more of an interesting thing that comes up during talking to other people in science, one of the professors I work with asked me why they didn’t measure glucocorticoid receptors (involved in stress). Apparently glucocorticoid receptors are also very important in the sleep wake cycle and cognitive performance, so if you’re in the field, here’s your golden idea you’ve been waiting for.

Final Thoughts

Even with current technology, it’s still difficult to look at the living human brain without damaging it. Sleep is also pretty hard to study, because it’s difficult to tell how similar sleep is between species. So I’m gonna say props to this study for doing what it can with what it has. I’m not sure whether the same things happen during normal sleep fluctuations, or how caffeine interacts with all of that, but that’s something for one of you readers out there to find out and for me to read in the future.

Have a science news article you want a closer look at? A concept you want to learn more about? Leave it in a comment or email us at phteatime@gmail.com!
About the author
14595564_10155083719871840_4974523626401782470_nMari is a graduate student studying psychology and neuroscience at the University of Minnesota. Her research focuses on affective, behavioral, and molecular aspects of opiate addiction. Mari loves all science and wants everyone else to be as excited about it and as critical of it as she is.
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