New clue to cause of human narcolepsy found

Scientists have found that an excess number of brain cells that produce the chemical histamine may play a key role in human narcolepsy - a disorder of the central nervous system characterised by uncontrollable periods of deep sleep.
Researchers at the University of California, Los Angeles Center for Sleep Research, in 2000, published findings showing that people suffering from narcolepsy had 90 per cent fewer neurons containing the neuropeptide hypocretin in their brains than healthy people.
Subsequent work by this group and others demonstrated that hypocretin is an arousing chemical that keeps us awake and elevates both mood and alertness; the death of hypocretin cells, the researchers said, helps explain the sleepiness of narcolepsy. But it has remained unclear what kills these cells.

Now, the same UCLA team has found that an excess of another brain cell type containing histamine may be the cause of the loss of hypocretin cells in human narcoleptics.
UCLA professor of psychiatry Jerome Siegel and colleagues reported in the journal Annals of Neurology that people with the disorder have nearly 65 per cent more brain cells containing the chemical histamine.
Their research suggests that this excess of histamine cells causes the loss of hypocretin cells in human narcoleptics.

Narcolepsy is a chronic neurological disorder caused by the brain's inability to control sleep-wake cycles. It causes sudden bouts of sleep and is often accompanied by cataplexy, an abrupt loss of voluntary muscle tone that can cause a person to collapse.

For the study, researchers examined five narcoleptic brains and seven control brains from human cadavers. Prior to death, all the narcoleptics had been diagnosed by a sleep disorder center as having narcolepsy with cataplexy.
These brains were also compared with the brains of three narcoleptic mouse models and to the brains of narcoleptic dogs.
The researchers found that the humans with narcolepsy had an average of 64 per cent more histamine neurons. The team did not see an increased number of these cells in any of the animal models of narcolepsy.
"Humans and animals with narcolepsy share the same symptoms, but we did not see the histamine cell changes we saw in humans in the animal models we examined," said Siegel, senior author of the research.

"We know that narcolepsy in the animal models is caused by engineered genetic changes that block hypocretin function. However, in humans, we did not know why the hypocretin cells die.
"Our current findings indicate that the increase of histamine cells that we see in human narcolepsy may cause the loss of hypocretin cells," he said.