"If these neurons are over-activated by environmental or mental stress in daily situations, they may support sustained arousal, triggering sleeplessness, leading to overeating," said lead author Tamas Horvath, associate professor in the Departments of Obstetrics, Gynecology & Reproductive Sciences (Ob/Gyn) and Neurobiology at Yale School of Medicine. "The more stress you have, the lower the threshold becomes for exciting these hypocretin neurons."

Horvath and co-author Xiao-Bing Gao, assistant professor in Ob/Gyn, studied hypocretin/orexin neurons in mice using electrophysiology and electron microscopy. They found a unique, previously un-described organization of inputs on hypocretin neurons in which excitatory nerve junctions outnumber inhibitory contacts by almost 10 fold. Stressors such as fasting further excite these neurons.

"This unique wiring and acute stress-induced plasticity of the hypocretin neurons correlates well with its involvement in the control of arousal and alertness, which are vital to survival," said Horvath. "But it may also be an underlying cause of insomnia and associated metabolic disturbances, including obesity. In addition, insomnia is characteristic of perimenopause (early onset of menopause), which may lead to increased prevalence of obesity in postmenopausal women."

Previous studies demonstrated the association between lack of sleep and obesity and suggested a good night's sleep to help obesity. Horvath found that the neurological basis of the link between obesity and insomnia make them both independent and related products of the overactivated hypocretin system. Therefore, he said, "people with weight and sleep
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Contact: Karen N. Peart
karen.peart@yale.edu
203-432-1326
Yale University
12-Apr-2005