Increase in Brain Cells with Histamine Linked to Narcolepsy

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MISSION HILLS, CA — An excess of a certain type of brain cell, those containing histamine, may be the cause of the loss of hypocretin cells which has been found in narcolepsy patients, according to a new study.

Previous studies by the team of researchers from the VA and the University of California Los Angeles (UCLA) showed that patients suffering from narcolepsy had 90% fewer neurons containing the neuropeptide hypocretin in their brains than healthy people. The death of hypocretin cells, which elevate mood and alertness, helped explain the sleepiness of narcolepsy, according to the researchers, but, until now, they did not know what killed the cells.

Jerome Siegel, PhD, chief of neurobiology research at the Sepulveda Veterans Affairs Medical Center in Mission Hills, CA, and his colleagues report in the Annals of Neurology that narcolepsy sufferers have nearly 65% more brain cells containing the chemical histamine.1

To reach their conclusions, researchers studied five narcoleptic brains and seven control brains from human cadavers who had been diagnosed prior to death as having narcolepsy with cataplexy. Those brains were also compared with the brains of three narcoleptic mouse models and to the brains of narcoleptic dogs.

“Our current findings indicate that the increase of histamine cells that we see in human narcolepsy may cause the loss of hypocretin cells,” said Siegel, who also is on the faculty at UCLA.

Study results also underscore the significance of brain plasticity, Siegel noted.

“This paper shows for the first time that neuronal numbers can increase greatly and not just serve as replacement cells,” he said. “In the current example, this appears to be pathological with the destruction of hypocretin; but, in other circumstances, it may underlie recovery and learning and open new routes to treatment of a number of neurological disorders.”

1. John J, Thannickal TC, McGregor R, Ramanathan L, Ohtsu H, Nishino S, Sakai N, Yamanaka A, Stone C, Cornford M, Siegel JM. Greatly increased numbers of histamine cells in human narcolepsy with cataplexy. Ann Neurol. 2013 Jul 2. doi: 10.1002/ana.23968. [Epub ahead of print] PubMed PMID: 23821583.

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