Losing Your Mind Without Sleep

The question of “why do we sleep?” has long been asked and has never been well understood. Despite it being a subject of study as early as the 1700’s (although probably earlier), there is still a lot of uncertainty surrounding our need to spend up to a third of our lives in an unconscious state. As suggested by Jessen et al. (2015), the 25% reduction in brain energy metabolism isn’t really enough to suggest that sleep is a means of energy conservation. When thinking on an evolutionary scale, sleep doesn’t make a whole lot of sense either as it leaves you in an extremely vulnerable state for attack by predators or enemy tribes. The first characterization of the glymphatic system by Iliff et at. (2012) helped to clear up our understanding of sleep as a time for the brain to do some housekeeping and clear out toxic metabolic waste products that are created while you are awake, but that still leaves many details to be described.

While some may approach the question of what happens during sleep by studying directly what goes on in your head at night, another good approach is to ask the question, “what happens if you DON’T sleep?” Bellesi et al. (2017) did just that, using mice as their study subjects. Their title, “Sleep loss promotes astrocytic phagocytosis and microglial activation in mouse cerebral cortex” essentially translates to “sleep loss makes your brain eat itself.” That doesn’t sound very pleasant, but the details are a little less dramatic. Let’s look a little more closely at what was found:

The study looked at both acute and chronic sleep deprivation (compared to control animals under normal sleep conditions). Acute sleep deprivation was achieved by keeping the animals awake for an additional 8 hours after their normal bedtime, while the chronic sleep deprivation group was kept awake for a full 4.5 days before sampling.

Researchers found increased levels of astrocytic phagocytosis in the synapses of the brains of both acute and chronic sleep-deprived mice. Astrocytes are housekeeping cells in the brain, and phagocytosis refers to their ability to clean up (or eat) damaged cells and other waste products. Given that we know sleep is a time for the glymphatic system to clear out metabolic waste from the brain, the astrocytes may just be performing the function of the glymphatic system (which is not active when you are awake). At least in the short term, this may be an ok substitute, but the authors only speculate on that point. So being sleep deprived does make your brain eat itself a little more than usual, but it’s probably mostly just eating damaged cells and other debris (although lack of sleep will also wear out your cells faster as they don’t have a chance to rest and recover, so the damaged cells being eaten may have been healthy cells if you had gotten to bed on time).

It was also found that in the chronic sleep deprivation group, microglial activation was elevated relative to both the control and acute sleep deprivation group. This could pose more of a problem, as microglia are generally associated with neuroinflammation. Interestingly, the authors found no evidence of increased neuroinflammation to go along with increased microglial levels, but they also acknowledge that their assays may not have been sensitive enough to detect low levels of inflammation. Regardless, they note that elevated levels of microglia leave the brain in a vulnerable state, making it “primed” for inflammation with the presence of any other stressor (a hit on the head, for instance).

As is the case with most studies, this one creates just as many questions as it answers and it would not be wise so simply project these results onto what happens to you under acute or chronic sleep deprivation. For one, you aren’t a mouse. For another, at least with the chronic sleep deprivation group, it’s not a good model of a stereotypical sleep-deprived person. Most people don’t go from normal sleep to 5 days straight with no sleep. Chronic sleep deprivation is generally just reduced sleep each night for longer periods of time (weeks, months, years on end). So the model depicted here may or may not be representative of a more prolonged sleep-reduced state.

Regardless, it is probably safe to say that the results presented by Bellesi et al. (2017) show that lack of sleep is not good for your brain (anyone who has ever been sleep deprived doesn’t need a study to tell them that!). While acute sleep deprivation may not be a huge issue, chronic sleep deprivation may (or may not) leave your brain in a susceptible state, making you more prone to things like concussions and dementia. Since everyone is different (and not a mouse), your individual brain health may require different amounts of sleep. That’s why it’s important to monitor your own brain health with a Brian Gauge to make sure that your specific lifestyle choices are optimizing your brain function.

So go get some sleep! But maybe not too much - apparently more than 8 hours of sleep per night will increase your risk of a heart attack.

References

Bellesi M, de Vivo L, Chini M, Gilli F, Tononi G, Cirelli C. Sleep loss promotes astrocytic phagocytosis and microglial activation in mouse cerebral cortex. Journal of Neuroscience. 2017.

Iliff JJ, Wang M, Liao Y, Plogg BA, Peng W, Gundersen GA, Benveniste H, Vates GE, Deane R, Goldman SA, Nagelhus EA. A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid β. Science translational medicine. 2012.

Jessen NA, Munk AS, Lundgaard I, Nedergaard M. The glymphatic system: a beginner’s guide. Neurochemical research. 2015.

Wang C, Bangdiwala SI, Rangarajan S, Lear SA, AlHabib KF, Mohan V, Teo K, Poirier P, TSE LA, Liu Z, Rosengren A. Association of estimated sleep duration and naps with mortality and cardiovascular events: a study of 116 632 people from 21 countries. European Heart Journal. 2018.