Science + Technology

UCLA/VA Researchers Pinpoint Role of Histamines in Waking


A study by scientists at the UCLA Neuropsychiatric Instituteand Veterans Affairs' Neurobiology Research Laboratory shows that brain cellscontaining the chemical histamine are critical for waking.

Detailed in the May 27 edition of the journal Neuron, thefindings show that the cessation of activity in histamine cells causes loss ofconsciousness during sleep, while cessation of activity in other brain cells —those containing the brain chemicals norepinephrine or serotonin — causes lossof muscle tone in sleep. The findings also help explain why antihistamines,often taken to control allergies, cause drowsiness.

"Our findings greatly improve our understanding of the brainactivity responsible for maintaining consciousness and muscle tone whileawake," said Dr. Jerome Siegel, senior author on the study. "The findingsshould aid in the development of drugs to induce sleep and to increasealertness." Siegel is a professor at the UCLA Neuropsychiatric Institute andchief of neurobiology research at the VA Greater Los Angeles Healthcare System,Sepulveda.

The research team conducted their study using dogs with thesleep disorder narcolepsy, in which sudden collapses of muscle tone, known ascataplexy, occur during waking. Although waking alertness is maintained duringcataplexy, muscle tone is lost.

In both narcoleptic and normal animals, cells containinghistamine, norepinephrine and serotonin are active in waking and inactive insleep. The researchers studied their activity in cataplexy to pinpoint theroles of the three cell groups in the loss of consciousness and loss of muscletone that occur during sleep.

The UCLA/VA researchers found that histamine cell activitycontinued during cataplexy, indicating that their activity is linked to waking.The team also found that norepinephrine and serotonin cell activity ceases incataplexy, showing that their activity is related to muscle tone, rather thanwaking.

In 2000 Siegel's team published its findings thatnarcoleptics had 95 percent fewer hypocretin (orexin) nerve cells in theirbrains than those without the illness. The study was the first to show apossible biological cause of narcolepsy.

The UCLA Neuropsychiatric Institute is an interdisciplinaryresearch and education institute devoted to the understanding of complex humanbehavior, including the genetic, biological, behavioral and socioculturalunderpinnings of normal behavior, and the causes and consequences ofneuropsychiatric disorders. More information about the Institute is availableonline at

The VA Greater Los Angeles Health Care System's NeurobiologyResearch Laboratory is a part of the Sleep Research Group. Thismultidisciplinary group of investigators is pursuing innovative ways to preventand treat sleep disorders. Current studies focus on body-temperature regulationduring sleep, brain mechanisms regulating sleep and circadian rhythms,narcolepsy and its causes, and the role of sleep in epileptic events.



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