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The Effects of Sleep Debt

Recent studies in humans and mice have shown that late nights and early mornings may cause long lasting damage to your brain.

The sleep debt collectors are coming. They want you to know that there is no such thing as forgiveness, only a shifting expectation of how and when you’re going to pay them back. You think of them as you lie in bed at night. How much will they ask for? Are you solvent? You fall asleep, then wake up in a cold sweat an hour later. You fall asleep, then wake up, drifting in and out of consciousness until morning.

As most every human has discovered, a couple nights of bad sleep is often followed by grogginess, difficulty concentrating, irritability, mood swings and sleepiness. For years, it was thought that these effects, accompanied by cognitive impairments like lousy performances on short-term memory tests, could be primarily attributed to a chemical called adenosine, a neurotransmitter that inhibits electrical impulses in the brain. Spikes of adenosine had been consistently observed in sleep-deprived rats and humans.

Adenosine levels can be quickly righted after a few nights of good sleep, however. This gave rise to a scientific consensus that sleep debt could be forgiven with a couple of quality snoozes — as reflected in casual statements like “I’ll catch up on sleep” or “I’ll be more awake tomorrow.”

But a review article published recently in the journal Trends in Neurosciences contends that the folk concept of sleep as something that can be saved up and paid off is bunk. The review, which canvassed the last couple of decades of research on long term neural effects of sleep deprivation in both animals and humans, points to mounting evidence that getting too little sleep most likely leads to long-lasting brain damage and increased risk of neurodegenerative disorders like Alzheimer’s disease.

“This is really, really important in setting the stage for what needs to be done in sleep health and sleep science,” said Mary Ellen Wells, a sleep scientist at the University of North Carolina, who did not contribute to the review.

It has long been known that intense periods of sleep deprivation are bad for your health. Forced insomnia was used for centuries as punishment and torture. In the first experimental study of sleep deprivation, published in 1894 by the Russian scientist Maria Manasseina, puppies were forced to stay awake through constant stimulation; they died within five days. Examining their bodies afterward, Manasseina observed that “the brain was the site of predilection of the most severe and most irreparable changes.” Blood vessels had hemorrhaged and fatty membranes had degenerated. “The total absence of sleep is more fatal for the animals than the total absence of food,” Manasseina concluded.

But there are many ways to not get enough sleep. You can go entirely without sleep for an extended period of time — what scientists call acute sleep deprivation. (In 1963, a high school student managed to stay awake for 264 hours.) You can consistently miss out on sleep — chronic sleep deprivation. You can lie awake, mind racing, or relax, watching television all night. Studies like Manasseina’s were seen as extreme to the point of being irrelevant to humans.

Research continued, but “that was where it was sort of pigeonholed,” said Fabian Fernandez, a neuroscientist at the University of Arizona who did not contribute to the new review. “When are you ever going to keep an animal or human awake until they die?”

Over the past couple of decades, however, the animal research on sleep deprivation has become more nuanced, precise and, possibly, applicable to humans, according to Dr. Sigrid Veasey, a neuroscientist at the University of Pennsylvania, and Zachary Zamore, a researcher in Dr. Veasey’s lab, the authors of the new review.

After surveying past studies of sleep-deprived mice, many of which Dr. Veasey conducted, the researchers found that when the animals were kept awake for just a couple of hours more than usual each day, two key parts of the brain were notably affected: the locus coeruleus, which manages feelings of alertness and arousal, and the hippocampus, which plays an important role in memory formation and learning. These regions, which, in humans, are central to sustaining conscious experience, slowed down the animals’ production of antioxidants, which protect neurons from unstable molecules that are constantly being produced, like exhaust fumes, by functioning cells. When antioxidant levels are low, these molecules can build up and attack the brain from inside, breaking down proteins, fats and DNA.

“Wakefulness in the brain, even under normal circumstances, incurs penalties,” Dr. Fernandez said. “But when you’re awake for too long, then the system gets overloaded. At some point, you can’t beat a dead horse. If you’re asking your cells to remain active for 30 percent more time each day, cells die.”

In the brains of mice, sleep deprivation led to cell death after a few days of sleep restriction — a much lower threshold for brain damage than previously thought. It also caused inflammation in the prefrontal cortex and increased levels of tau and amyloid proteins, which have been linked to neurodegenerative diseases like Alzheimer’s and Parkinson’s, in the locus coeruleus and hippocampus.

After a full year of regular sleep, the mice that previously had been sleep-deprived still suffered from neural damage and brain inflammation. To Dr. Veasey and Mr. Zamore, this suggested that the effects were long-lasting and perhaps permanent.

Nevertheless, many scientists said that the new research should not be cause for panic. “It is possible that sleep deprivation damages rat and mouse brains, but that doesn’t mean that you should get stressed about not getting enough sleep,” said Jerome Siegel, a sleep scientist at the University of California, Los Angeles, who did not contribute to the review.

Dr. Siegel noted that neural injury comes in degrees, and that the extent of sleep deprivation’s effect on the human brain is still largely unknown. He also expressed concern that undue worry about the long-term effects of sleep deprivation could lead people to try to sleep more, unnecessarily and with medication.

“The simplest message is sleep deprivation is bad, but that doesn’t mean that sleep is monotonically good,” he said.

There is currently no ethical way to measure the degree and kind of cell damage caused by sleep deprivation in the locus coeruleus and hippocampus of a living human. Instead, longitudinal studies published over the past 15 years have relied on behavioral changes and self-reported sleep data to link chronic bad sleep to dementia, depression, metabolic issues, cardiovascular disease, insufficient immune response and even lower grade-point averages. These experiments can be difficult to confirm, but, taken together with findings in animal models, they hint that there is some sort of long-term relationship between a lack of sleep and physical and cognitive damage.

“Sleep loss can injure the brain, and if it happens in mice, and it has been shown to happen in other species, then it probably does happen in humans,” Dr. Veasey said. “It always begs the question: How much sleep loss would cause injuries? But looking at all of this literature together, of around one week of chronic sleep loss, it really does suggest that you injured the brain to some extent.”

If a link can be drawn between mice and humans, it could change the way we think about sleep, which is typically in terms of sleepiness rather than neural damage. There is already a known gap between how people perceive their own cognitive capacities after sleep deprivation and how they actually perform on memory and reaction time tests. People can feel fine while their brains are in turmoil, and they can feel exhausted when their brains are fine. “Perception and reality of your sleep can be very, very different,” Dr. Wells said.

That disconnect, in turn, “has actually hampered our asking the right questions,” Dr. Veasey added. Her hope is that people and scientists will come to understand sleep more fully. And then, informed, we’ll no doubt go into sleep debt anyway.

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