Just one night can revive the brain and reverse the feeling of depression for days

Have you ever pulled an all-nighter and ended up feeling wired, hyper, even a little drunk? Well, scientists are trying to harness that feeling to see if it might help people suffering from depression, and a new study in mice has revealed the changes in the sleep-deprived brain that cause it.

For most of us, the thought of having to give up a night of restful sleep is not a happy one. But when they’re forced to wake up with a night shift, a long commute, or a last-minute study session, many people find they feel surprisingly upbeat the next day. You can describe it as feeling tired and heavy, or dizzy, or even a little delirious (but in a good way).

If just one night can have this effect, the scientists concluded, it could help us better understand how the brain changes to affect our mood and how some antidepressants, like ketamine, can work so quickly.

“It’s interesting that mood changes after acute sleep loss are so real, even in healthy subjects, as I and many others have experienced,” said Mingzheng Wu, a postdoctoral fellow at Northwestern University and first author of the new study on sleep deprivation, in statement. . But the exact mechanisms in the brain that lead to these effects remain poorly understood.

To learn more, Wu and his team performed experiments on healthy adult mice. They devised a system to keep the animals awake while minimizing the amount of stress they were under, using an enclosure with a raised platform above a slowly rotating beam. The mice could either cool off on the platform, or go explore below, but they had to keep moving to avoid the rays. The authors tested the device and found that when the mice were housed in it, they slept significantly less.

After a night without sleep, the authors observed how the mice behaved in a more aggressive and hypersexualized manner. The culprit? Dopamine: the reward neurotransmitter.

The authors could see that dopamine signaling was increased in the animals’ brains, but they weren’t sure if it was specific to certain regions or a brain-wide effect. They took a closer look at four regions, the prefrontal cortex, nucleus accumbens, hypothalamus and dorsal striatum, monitoring them for dopamine release and then silencing them one by one.

The antidepressant effect persisted except when we muted dopamine input to the prefrontal cortex, explained senior author Yevgenia Kozorovitskii. This means that the prefrontal cortex is a clinically relevant area when seeking therapeutic targets. But it also reinforces an idea that has recently developed in the field: dopamine neurons play very important but very different roles in the brain. They are not just this monolithic population that simply predicts rewards.

This point about therapeutic goals is crucial. According to the Centers for Disease Control and Prevention (CDC), depression affects 16 million American adults each year, and antidepressants are widely used. While some people find traditional antidepressants transformative, they don’t work for everyone and can have significant side effects. Studies are exploring the potential of new approaches, such as psychedelics, for the most difficult-to-treat cases, but there is always a need for better understanding that could lead to new therapies.

That doesn’t mean, however, that Kozorovitsky would recommend an all-nighter as a quick fix. Organisms may have developed this state of heightened awareness during times when sleep delay and high alertness could protect them from predators and other threats, but over time the problems of chronic sleep deprivation will quickly begin to outweigh these benefits.

However, it is an important new avenue for researchers to continue to explore.

We found that sleep loss causes a powerful antidepressant effect and reprograms the brain, Kozorovitskii said. This is an important reminder of how our casual activities, like a sleepless night, can fundamentally change the brain in just a few hours.

The study was published in the journal Neuron.

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