Lack of sleep in mice sends their brains into overdrive — making them “cleaner” in the short run, but causing brain damage in the long run.

Image via Max Pixel.

Burning the midnight oil might burn your brain itself. We all like to “steal” as much as possible from the day, but sleep is a price we simply have to pay for our bodies functioning, and trying to cheat sleep only ends up cheating yourself. Michele Bellesi of the Marche Polytechnic University in Italy wanted to see what effects sleep deprivation has on our brains, so she tried to simulate it on mice.

Basically, Bellesi found that in the short run, chronic sleep deprivation can actually be beneficial, clearing potentially harmful debris and rebuilding worn circuitry might protect healthy brain connections. However, in the long run, the brain goes into overdrive and starts destroying worn-out cells and putting people at a risk of Alzheimer’s and other neurological disorders.

Sleeping the garbage away

Sleeping is a complex phenomenon, still poorly understood. We do know that sleeping is much more than just the body replenishing its energy levels. For instance, research has shown that during sleep, the brain sweeps away the toxic byproducts of neural activity from the day. It’s like taking out the garbage inside your brain. Well, that process also takes place, even more intensely, when you’re chronically sleep deprived — which is bizarre in the first place and we don’t really know why this happens. But after a while, the damage starts to set in, affecting both neurons (the brain cells) and synapses (the connections between the brain cells); once that happens, even recovering the sleep isn’t really clearing the damage.

This happens because like all cells inside our body, neurons are “cleaned up” by glial cells, namely the microglial cells. These are the first and main form of active immune defense in the central nervous system. Synapses are maintained by astrocytes, which among other functions, prune unnecessary synapses and corrects their shape. These processes happen mostly when we sleep. What this study found is that they happen even faster when we don’t sleep enough — the brain “cleans” too much of itself, and starts devouring itself. It’s an unexpected discovery.

“We show for the first time that portions of synapses are literally eaten by astrocytes because of sleep loss,” says Bellesi.

An astrocyte cell grown in tissue culture stained with antibodies to be more visible. Image credits: GerryShaw / Wikipedia.

The finding could explain why a lack of sleep seems to make people more vulnerable to developing Alzheimer’s or similar conditions says Agnès Nadjar of the University of Bordeaux in France. Researchers are now investigating whether there is some way of repairing the damage, but the takeaway is pretty clear (and you can tell this to kids if you’re having problems sending them to sleep): if you don’t sleep enough, your brain will start to eat itself.

To our knowledge, this is the first study to show how these processes occur during sleep deprivation. It’s not clear if they are replicated on humans.

“We find that astrocytic phagocytosis, mainly of presynaptic elements in large synapses, occurs after both acute and chronic sleep loss, but not after spontaneous wake, suggesting that it may promote the housekeeping and recycling of worn components of heavily used, strong synapses,” the researchers report. “By contrast, only chronic sleep loss activates microglia cells and promotes their phagocytic activity … suggesting that extended sleep disruption may prime microglia and perhaps predispose the brain to other forms of insult.”

Journal Reference: Michele Bellesi, Luisa de Vivo, Mattia Chini, Francesca Gilli, Giulio Tononi and Chiara Cirelli — Sleep Loss Promotes Astrocytic Phagocytosis and Microglial Activation in Mouse Cerebral Cortex. Journal of Neuroscience 24 May 2017, 37 (21) 5263-5273; DOI: https://doi.org/10.1523/JNEUROSCI.3981-16.2017