Concomitant loss of dynorphin, NARP, and orexin in narcolepsy NEUROLOGY Crocker, A., Espana, R. A., Papadopoulou, M., SAPER, C. B., Faraco, J., Sakurai, T., Honda, M., Mignot, E., Scammell, T. E. 2005; 65 (8): 1184-1188


Narcolepsy with cataplexy is associated with a loss of orexin/hypocretin. It is speculated that an autoimmune process kills the orexin-producing neurons, but these cells may survive yet fail to produce orexin.To examine whether other markers of the orexin neurons are lost in narcolepsy with cataplexy.We used immunohistochemistry and in situ hybridization to examine the expression of orexin, neuronal activity-regulated pentraxin (NARP), and prodynorphin in hypothalami from five control and two narcoleptic individuals.In the control hypothalami, at least 80% of the orexin-producing neurons also contained prodynorphin mRNA and NARP. In the patients with narcolepsy, the number of cells producing these markers was reduced to about 5 to 10% of normal.Narcolepsy with cataplexy is likely caused by a loss of the orexin-producing neurons. In addition, loss of dynorphin and neuronal activity-regulated pentraxin may contribute to the symptoms of narcolepsy.

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