Profs Probe the Science of Sleep

Part one of a four-part series.

Every night, our bodies become paralyzed for brief spells, our eyes dart rapidly under closed eyelids, and we’re forced to watch hallucinogenic episodes that we call dreams. These visions make little sense. You could be, say, riding a bike, and then suddenly you’re swimming, and then riding a bus down a highway in a foreign country, about to crash — and it doesn’t occur to you that this is, to say the least, illogical. Odder still, all mammals experience this nighttime scenario (minus the bike riding). Dreaming is something that all of us do, but none of us knows why we do it.

The question why do we dream? has perplexed scientists ever since REM, or rapid eye movement, sleep was first scientifically described in 1953. And it’s not the only sleep-related riddle. “The major problem is that we do not know the physiological function of sleep,” says Irina Zhdanova, an associate professor of anatomy and neurobiology at the School of Medicine.

In an age of discoveries about the building blocks of matter and the nature of time and space, the purpose and mechanism of sleep remain poorly understood, but Zhdanova and other researchers at Boston University are making inroads, one night at a time.

There are good reasons for trying to figure out sleep’s secrets. Research has shown that enough sleep can make you smarter, improve your memory, lower your odds of getting cardiovascular disease and diabetes, and help you feel better and recover from illness more quickly. It’s better than any blockbuster drug Big Pharma might come up with, and cheaper too, but how it works and what happens when we don’t — or can’t — get our Zs continue to puzzle scientists.

Take what seems like a simple question: how do we fall asleep? Zhdanova is studying the effects of melatonin, a naturally occurring hormone produced by the brain’s pineal gland, on circadian rhythms, one mechanism of sleep regulation. Circadian rhythms are our sleep cycles, which typically are slightly more than 24 hours. “Under normal conditions, depending on when we go to bed, we will start secreting melatonin at night,” Zhdanova says. “It brings this circadian signal — what the time of day is — to every cell in the body.” Earlier studies she conducted while she was at MIT showed that in certain concentrations melatonin has a distinct sleep-inducing effect on humans. Production of the hormone slows as daybreak approaches, and then stops; it’s also suppressed if the light is turned on in the middle of the night.

Zhdanova and her colleagues are trying to find out how melatonin promotes sleep by studying the behavior of zebrafish. In her Medical Campus laboratory, thousands of little striped fish swim around in hundreds of small blue tanks. She has been measuring the effects of melatonin on the fish, using sophisticated analyses to determine the pathways it takes in their brains. She monitors the effects of varying levels of melatonin by filming holding areas in a small tank. Typically, 10 fish are observed by a single camera, with all movements simultaneously plotted by a computer program in real time. Researchers can watch their movements on the computer monitor: slow movements are sketched in green lines, rapid ones in red, and stillness in white.

The melatonin is put into the tanks in drops, so it is equally dispersed to all the fish, which absorb it quickly into their bodies, or the hormone is suppressed either through a genetic switch or by using constant bright light. “When we check pharmacologically and with environmental light, we know the activity is increased if we suppress melatonin,” Zhdanova says. “So that suggests that melatonin at night normally keeps activity at bay. And it’s a very clear effect because when we administer melatonin at any time of day, it will inhibit the fish locomotor activities.”

Does this mean that if we have trouble getting to sleep, we should start popping melatonin pills? Not exactly, Zhdanova says. “I’m very much for use of melatonin under medical supervision — I think it’s very useful.” She cautions, though, that self-medicating with melatonin isn’t the way to go. “When I was still working with humans, I was very much concerned that the market for melatonin is unregulated, in two ways. First, the doses are extremely high” — up to 10 times as high as they should be. Plus, the Food and Drug Administration “doesn’t control the quality of it — nobody really measures how much melatonin there is [in the pills]. Several labs, including mine, measured various preparations, and we found it was often more or less than it was claimed — sometimes down to zero,” she says.

“We don’t even realize in how many areas it might be useful,” she adds. Only some sleep disorders respond to melatonin, though, and in fact, some individuals are more sensitive to melatonin than others.

Zhdanova is also looking into the difference that aging makes in sensitivity to melatonin. “I am interested to see how much, for example, with aging, the numbers of melatonin receptors change in different areas of the brain. It might be that, for example, in other places it’s fine, but here, where you really need it, the number is lower.”

Melatonin also seems to affect cognitive performance, she says, but it’s unclear exactly how that happens. Is it because with increased melatonin people sleep better and thus have better attention, or does it have a direct effect outside the sleep mechanism? “I’m very much interested in the overall effect of melatonin,” she says, “and because I’m a physician originally, I always think about how this can be useful to humans, to patients.”

Check BU Today tomorrow for part two of "Profs Probe the Science of Sleep."

This article originally ran in the Winter 2006–2007 edition of Bostonia.

Taylor McNeil can be reached at tmcneil@bu.edu.