Histamine is key to narcolepsy

Scientists studying an animal model of narcolepsy have found that histamine-activated brain cells are key to wakefulness. The study was funded in part by the National Institute of Neurological Disorders and Stroke (NINDS) and appeared in the journal Neuron.

Narcolepsy is a disorder of sleep regulation that affects control of wakefulness and sleep and renders the patient subject to disabling sleepiness during the day. Some patients also have episodes of cataplexy, in which they suddenly lose muscle tone and go limp for up to 30 seconds but remains fully conscious. Cataplexy resembles wakefulness in that consciousness is preserved and also resembles REM sleep — a deep sleep in which most of our dreams occur — in that the individual loses muscle tone.

Researchers previously thought that brain cells that use serotonin, norepinephrine, and histamine to transmit nerve impulses acted identically in regulating sleep and arousal, with chemical levels being high during wakefulness and reduced during sleep. (Histamine, a neurotransmitter and a hormone, occurs naturally in the body. Histamine-containing neurons are found in the hypothalamus and project into the areas of the brain that are involved with sleep, memory, emotion, and temperature.)

Studying dogs that are specially bred to carry a genetic form of narcolepsy, lead investigator Jerome Siegel, Ph.D., of the University of California-Los Angeles, and colleagues examined histamine brain cell activity when the dogs were in cataplexy and during REM sleep. The team found that histamine neuron activity continued during cataplexy but ceased during sleep, showing that the chemical was key to waking. The scientists also found that serotonin and norepinephrine neuron activity were high during wakefulness but shut off during sleep and cataplexy, causing the loss of muscle tone seen in both conditions.

The findings also show why antihistamines, commonly used to treat colds and allergies, cause drowsiness and impair alertness.

"Our findings greatly improve our understanding of the brain activity responsible for maintaining consciousness and muscle tone while awake," said Dr. Siegel. "These findings should aid in the development of drugs to induce sleep and increase alertness."

"These findings are interesting both scientifically and pharmacologically," said Merrill Mitler, Ph.D., NINDS' program director for sleep research. "Many over the counter sleep remedies currently contain antihistamines and can be quite sedating, but don't necessarily promote natural sleep. A better understanding of the chemical interactions involved with wakefulness and sleep may lead to new treatments that counter daytime sleepiness and offer satisfying sleep for persons with sleep problems such as insomnia."

The NINDS is a component of the National Institutes of Health within the Department of Health and Human Services and is the nation's primary supporter of biomedical research on the brain and nervous system.