VA/UCLA researchers pinpoint role of histamines in waking

A study by scientists with the Veterans Affairs’ Neurobiology Research Laboratory and UCLA Neuropsychiatric Institute shows that brain cells containing the chemical histamine are critical for waking.

Detailed in the May 27 edition of the journal Neuron, the findings show that the cessation of activity in histamine cells causes loss of consciousness during sleep, while cessation of activity in other brain cells–those containing the brain chemicals norepinephrine or serotonin–causes loss of 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 brain activity responsible for maintaining consciousness and muscle tone while awake,” said Dr. Jerome Siegel, senior author on the study. “The findings should aid in the development of drugs to induce sleep and to increase alertness.” Siegel is chief of neurobiology research at the VA Greater Los Angeles Healthcare System, Sepulveda, and a professor at the UCLA Neuropsychiatric Institute.

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

In both narcoleptic and normal animals, cells containing histamine, norepinephrine and serotonin are active in waking and inactive in sleep. The researchers studied their activity in cataplexy to pinpoint the roles of the three cell groups in the loss of consciousness and loss of muscle tone that occur during sleep.

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

In 2000, Siegel’s team published its findings that narcoleptics had 95 percent fewer hypocretin (orexin) nerve cells in their brains than those without the illness. The study was the first to show a possible biological cause of narcolepsy.

The VA Greater Los Angeles Health Care System’s Neurobiology Research Laboratory is a part of the Sleep Research Group. This multidisciplinary group of investigators is pursuing innovative ways to prevent and treat sleep disorders. Current studies focus on body-temperature regulation during sleep; brain mechanisms regulating sleep and circadian rhythms; narcolepsy and its causes; and the role of sleep in epileptic events.

The UCLA Neuropsychiatric Institute is an interdisciplinary research and education institute devoted to the understanding of complex human behavior, including the genetic, biological, behavioral and sociocultural underpinnings of normal behavior, and the causes and consequences of neuropsychiatric disorders. More information about the Institute is available online at www.npi.ucla.edu.