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Hopkins team explores the dark side of light

Scientists who study sleep understand that light has a dark side, because it can interrupt natural rhythms, causing the mood and learning problems that go with lack of rest. Johns Hopkins University researchers have taken the understanding a step further and to a cellular level, finding that exposure to bright light at night appears to create these problems by itself, even apart from sleep patterns.

Since the research was published online weeks ago in the journal Nature, biology professor Samer Hattar, who led the research team, has been much in demand as a speaker. It seems the connection between light exposure and mood has sparked considerable interest, he said.

"Once you start talking about depression, it's clearly a different ballgame," said Hattar, back from a presentation the day before at the Carnegie Institution for Science on the Hopkins campus, and two weeks before that at Emory University in Atlanta.

At the very least, the work suggests that people would be better off lowering lights at night, and choosing light from the red end of the spectrum — all of which recommends against nighttime overexposure to computer screens, iPads and gadgets that glow cool blue. A scholar on the biological basis of psychiatric disorders also said the research could lead to development of more effective anti-depressant medications.

Hattar, a specialist in the biology of circadian rhythm — any biological process that works on roughly a 24-hour cycle — was sitting in his office at Mudd Hall, where the bluish overhead light is quite bright . The room is a couple of floors above the basement, where scores of brownish-gray mice live in an array of light conditions, their cages in brightness and in pitch dark wired to computers tracking them running their wheels.

By tracking the mice, and the action of a type of cell in the eye that was not identified with certainty until 2002, the team discovered something about how light affects both mice and humans. In many respects the two are alike.

Both have the "rods" and "cones" structures in the retina that have been understood since the 19th century as the sole light receptors. Both also have a third, apparently more primitive type of cell whose light sensitivity was dismissed by scientists for years, but confirmed in research published 10 years ago jointly by David Berson of Brown University and Hattar, who gives all the credit to his partner. It's now accepted that these cells called "intrinsically photosensitive retinal ganglion cells," or "ipRGCs," do react to light.

These cells, resembling tree branches, are eccentric actors.

They do not "see," images, as the rods and cones do, but they sense light, particularly light from the blue end of the spectrum, and have been linked to an array of body functions. It's believed they play a role in regulating circadian rhythm and sleep, and, according to an article published this year in Discover magazine, may explain the connection between exposure to bright light and migraine headaches, and the association of mood depression with winter's longer periods of darkness.

Hattar and Berson found that these cells contain melanopsin, a light-sensitive pigment found in the ganglion layer of the retina in 2000. Hattar has been on the case for more than a decade, trying to understand what these ipRGCs do.

The experiments published recently in Nature are part of that inquiry, Hattar said, giving much of the credit to doctoral student Tara A. LeGates and Cara M. Altimus, a post-doctoral researcher at the School of Medicine.

Hattar's team kept some mice on a seven-hour cycle split 50-50 between light and dark. This cycle was found not to disrupt sleep or circadian rhythms, but as it is considered an abnormal light cycle for these nocturnal creatures, it would show the effect of aberrant light exposure itself.

Compared with mice kept on a 24-hour cycle split 50-50, the mice on the seven-hour routine were not happy. They weren't as active and showed less interest in sugar — both signs of depression. They also showed higher levels of the hormone corticosterone, which has been established as linked to both depression and learning difficulties. The test mice also did not perform as well on a learning task.

Given Prozac, the test mice perked up, and did better on the learning task.

Lisa Monteggia, a scholar on the biological basis of neuropsychiatric disorders at the University of Texas Southwestern Medical Center in Dallas, said the research is "important in two major aspects." For one thing, it suggests a biological explanation for the link between light cycles and depression, a phenomenon that is commonly observed but not well understood.

Also, by inducing depression in a way that is not typical in the research, the work "may help uncover unexpected therapeutic targets for depression and help the design of faster-acting and more reliable antidepressants."

Hattar said the work is raising new questions as researchers learn more about those ipRGCs: "How does the retina influence the brain to cause increases in corticosterone to influence depression/learning? Is there a better time of day to be exposed or stay away from light?"

In the meantime, he said, he would suggest caution about nighttime overexposure to the light of fluorescent lamps and the bright bluish allures of Facebook, YouTube and Twitter.

arthur.hirsch@baltsun.com

Samer Hattar

Johns Hopkins University professor with joint appointment, Departments of Neuroscience, Biology

Postdoctoral Fellow, Johns Hopkins University School of Medicine, Howard Hughes Medical Institute

Doctorate, University of Houston.

Master's degree, American University of Beirut

Undergraduate degree, Yarmouk University, Jordan

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