DARIEN, IL – A new study provides surprising evidence that people with narcolepsy have an increased number of neurons that produce histamine, suggesting that histamine signaling may be a novel therapeutic target for this potentially disabling sleep disorder.
"The orexin/hypocretin neuropeptides promote wakefulness, and researchers have known for 13 years that narcolepsy is caused by loss of the orexin/hypocretin neurons in the hypothalamus," said principal investigator Thomas Scammell, MD, professor of Neurology at Beth Israel Deaconess Medical Center in Boston, Mass. "We found that narcolepsy is also associated with a very large increase in the number of neurons producing histamine, another wake-promoting neurotransmitter."
The study involved counting the number of hypothalamic neurons producing orexin, melanin-concentrating hormone and histamine in seven narcolepsy patients and 12 patients that served as a control group. The researchers also examined these systems in mouse models of narcolepsy (six orexin/ataxin-3 transgenic mice and five orexin ligand knockout mice, compared to six wild-type mice).
Results show that narcolepsy patients had 94 percent more histaminergic tuberomammillary nucleus (TMN) neurons. This increase was more pronounced in five narcolepsy patients with severe orexin neuron loss compared to two patients with less severe loss. Likewise, the number of histaminergic TMN neurons was increased 53 percent in orexin ligand knockout mice compared to wild type mice, while orexin/ataxin-3 transgenic mice showed an intermediate 28 percent increase.
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