My friend Dragana published a beautiful and important study yesterday, potentially explaining a 50 years old mystery: why do some animals die when forced to stay awake for days or weeks? The study was led by talented postdoc Alexandra Vaccaro (thread)
cell.com/cell/fulltext/…
cell.com/cell/fulltext/…
Last year, @BeckwithEsteban and @qgeissmann in my lab addressed a related and equally puzzling question: is sleep a fundamental and vital biological function? A few people reached, asking me how to piece the 2 studies together. It's easy. Let's do it.
advances.sciencemag.org/content/5/2/ea…
advances.sciencemag.org/content/5/2/ea…
First of all, it's important to clarify that the 2 studies address 2 fascinating but different questions: we asked "can an animal survive without sleep?"; Alexandra asked "why do some animals die after chronic sleep deprivation?". Both studies use fruit flies as the main model.
As @vero_greenwood explained well in her brilliant piece (quantamagazine.org/why-sleep-depr…) lethality upon sleep deprivation was first found in dogs at the end of 19th century, using gruesome techniques (😢) that would not be ethically acceptable by today standards . Dogs died miserably.
However, those techniques were poorly controlled so Allan Rechtschaffen worked really hard to try and reproduce them in rats using a more controlled environment. He invented the "disk over water" system to try and control stress a bit more (Image from www-personal.umich.edu/~ojwalch/sleep…)
In the DoW, when the experimental animal (right) falls asleep the disk rotates and the animal ends up in the water. If the poor mouse falls asleep, the disc rotates and it will fall in the water - which the rat hates! The control rodent (left) can sleep when its sibling is awake.
Rechstaffen published these findings in a seminal paper in 1983 science.sciencemag.org/content/221/46… and dedicated his career to try to understand why the animal would die. Was related to lack of sleep per se? Or was it an indirect cause, like a decline of immune response? He never found out.
The finding was important and led to the popular misconception that sleep deprivation would eventually lead to death in humans. We actually don't know whether this is the case, because an experiment to check that cannot really be done for obvious ethical reasons!!
But rats certainly do die. Why? Dragana's and Alexandra's paper suggests it is because sleep deprivation leads - directly or indirectly - to the accumulation of oxidants in the guts and that's not good for health. (Eat your fruit!)
Even though they could not replicate those old rat experiments for ethical reasons, they found flies die with sleep deprivation unless they were fed with antioxidants. Cool!
In our paper, however, we found we could not really kill the flies with sleep deprivation so why this difference? I can think of 2 explanations:
1) Inspired by the "disc over water" system, in our paper we tried to intervene as little as possible and we adopted a system in which flies are challenged only when they fall asleep, with a 1-second rotation of the tube.
In their paper, Alexandra and Dragana thermogenetically activate neurons that lead to an increase in activity or, alternatively, use mechanisms of mechanical agitations similar to the one in video below
2) Alexandra and Dragana show that their flies die after a few days of treatment. UNLESS they are fed with antioxidants! In which case, they live - like we previously showed.
What does it mean? Perhaps the different techniques employed have different capabilities in creating ROS. Perhaps it's not WHETHER you lose sleep, but HOW you lose sleep. Could ROS accumulation be a consequence of the constant activity or of exhaustion?
Or perhaps our flies had an "Italian" diet and already had some natural antioxidants in their meal? imperial.ac.uk/fly-forum/prot…
In any case, I hope I explained why both papers are not in contradiction (we both get long-living flies!!!), why both are important and - above everything else - I hope it is clear why flies are the best animal model ever to study physiology and biology! GO FLIES.
