By LEE BOWMAN
Scripps Howard News Service
April 12, 2005
Insomnia, a chronic inability to fall asleep or stay asleep, is estimated to affect as many as one in eight Americans. Other recent research has found that the less people sleep, the more likely they are to gain weight, apparently because the lack of sleep triggers hormone imbalances that boost the desire to eat.
Now, in a study using mice and human cells, researchers at Yale University's School of Medicine found that specialized brain cells called hypocretin neurons are particularly susceptible to over-stimulation and lack the ability of most other neurons to filter out signals from other regions of the brain that aren't meant for them.
"The cell bodies of most neurons act as a filter," sorting through a multitude of signals to eliminate noise and generate an appropriate response, said Tamas Horvath, an associate professor of reproductive neuroscience and co-author of the study, published Tuesday in the April issue of the journal Cell Metabolism. "But it appears that the basic wiring of hypocretin neurons allows noise to become the major signal."
"If these neurons are over-activated by environmental or mental stress in daily situations, they may support sustained arousal, triggering sleeplessness, leading to overeating," Horvath said. "The more stress you have, the lower the threshold becomes for exciting these hypocretin neurons."
By finding ways to moderate this wiring, scientists may be able to find new treatments for insomnia and other sleep disorders. Natural variations in this brain system may also explain differences among people in how easily their sleep is disturbed.
Scientists discovered the hypocretin cells several years ago while studying narcolepsy, a condition marked by sudden, involuntary lapses into deep sleep. It's now known that narcolepsy stems from a shortage or malfunction of hypocretin cells.
Horvath and colleague Xiao-Bing Gao carried out experiments using human brain slices and lab mice to look at how the brain cells are organized and linked to the rest of the brain.
The researchers found that, with humans and mice, each cell has 10 times more nerve junctions that stimulate them than inhibitory contacts. And overnight deprivation of food promoted the formation of even more "excitatory" inputs, they found. But once the mice were fed, the inputs reversed, indicating the responsiveness of the hypocretin system to prevailing conditions.
"This unique wiring and acute stress-induced plasticity (of the hypocretin system) correlates well with its involvement in the control of arousal and alertness, which are vital to survival," Horvath said.
In nature, an animal - whether mouse or human or whatever - that misses a meal has better odds of survival by staying awake to look for food, so "in an evolutionary sense, the response of the hypocretin system to small stimuli would have been necessary," he added. "But in today's chronically stressful environment, the circuitry may also be an underlying cause of insomnia and associated metabolism disturbances, including obesity."
Although his research may eventually yield new ways to manipulate the human brain, for now, Horvath said, "people with weight and sleep problems could benefit from cutting back on the stressful aspects of their lives, rather than trying to specifically medicate either insomnia or obesity."
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