Baltimore Sun

‘Catching up’ on sleep not recommende­d

Review says concept of saving up and paying off shut-eye is hooey

- By Oliver Whang

As most every human has discovered, a few 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 shortterm memory tests, could be primarily attributed to 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 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 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 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 Veasey’s lab, the authors of the new review.

After surveying past studies of sleep-deprived mice, many of which

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,” 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% 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 sleepdepri­ved still suffered from neural damage and brain inflammati­on. To Veasey and Zamore, this suggested that the effects were long-lasting and perhaps permanent.

But 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.

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,” 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.”


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