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UCI study could eventually help people with sleep disorders, researchers say

A study led by UC Irvine scientists involving animals may someday lead to treatments for people with insomnia and other sleep disorders, the researchers say.

As the team — led by Qun-Yong Zhou, a UCI professor of pharmacology — studied the sleeping and waking patterns of mice and monkeys, the group determined that the patterns were not governed by a specific portion of the brain commonly thought to be the body’s “master clock.”

Instead of the suprachiasmatic nucleus, or SCN, directing the body to sleep or wake up, the researchers found that light being processed through the animals’ eyes played a much bigger role.

While the mice in the study — which are nocturnal, meaning they are active at night — and the monkeys — which are diurnal, meaning they are active during the day — process light through their eyes in a similar way, the signals triggered by the light that regulate sleep and awake states travel through different routes to the brain, causing one type of animal to sleep during the day and the other to sleep at night.

“This has major implications for sleep disorders and even mood disorders,” Zhou said. “It’s something we’re considering for sleep treatments for humans.”

By understanding the “wiring” that sleep and awake signals travel within monkeys’ brains, scientists can better understand the nature of the same signals that move within a human brain, the professor said.

The study says that for monkeys, the closest living relative to humans, light travels into the retinal ganglion cells, or ipRGC, which send a signal to the super colliculus, a part of the brain that tells the body to become alert and attentive.

For the mice, the path is different. Light travels into the ipRGC, which deliver a signal to the SCN telling the animals to go to sleep.

A human who experiences insomnia is not wired similarly to mice, Zhou said, but instead the super colliculus may not be as receptive to the signals, possibly preventing the body from entering a sleep mode.

When first embarking on the study more than 10 years ago, the research team meant to discover why nocturnal animals are active at night while diurnal ones are active during the day.

For years, the group sought to find a “switch” they believed the SCN triggered to signal the animals to sleep or awaken, but nothing of the sort was uncovered.

Then they decided to observe how the animals responded to light.

“We eventually found that the SC [super colliculus] patterns were different,” Zhou said.

Other studies, he noted, have determined the SCN to be the body’s master clock but that his team’s findings are overturning that long-held view.

“It’s possible that the ipRGC is the master clock,” he added. “For a long time, we had no idea that the ipRGC had anything to do with this. But we are scientists. When we find that one thing doesn’t explain, then maybe there’s another thing that will.”

Christopher Colwell, a colleague of Zhou’s and a professor in the psychiatry department of UCLA Medical School, said he finds the team’s research compelling, though he still considers the SCN to be the body’s timekeeper.

“There’s overwhelming evidence that the SCN in the hypothalamus is the master clock, but that doesn’t mean there’s not an important role in the retinas,” said Colwell, who also researches sleep and circadian rhythms. "[Their research] is exciting because, first, it’s giving us new information on what’s different between day-active and night-active animals and, second, it has the potential to have a drug that can impact us in a beneficial way. Yes, it has implications for humans — not immediately, but down the line. It is definitely promising.”

The team now plans to use its research to explore possible sleep treatments for people and will try to determine whether it’s possible to redirect the signaling patterns in the brain.

“Can you make an animal less nocturnal? Or can you convert the animal to sleep at night?” Zhou said. “These are some of the questions we have.”

alexandra.chan@latimes.com

Twitter: @AlexandraChan10


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