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Published online before print June 15, 2005, doi:10.1212/01.WNL.0000168173.71940.ab)
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Received December 30, 2004
Accepted March 15, 2005

Concomitant loss of dynorphin, NARP, and orexin in narcolepsy

A. Crocker BS, R. A. España PhD, M. Papadopoulou BS, C. B. Saper MD, PhD, J. Faraco PhD, T. Sakurai MD, PhD, M. Honda MD, PhD, E. Mignot MD, PhD, and T. E. Scammell MD*

From the Department of Neurology (A. Crocker and M. Papadopoulou, and Drs. España, Saper, and Scammell), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA; Department of Psychiatry (Drs. Faraco, Honda, and Mignot), Stanford University Center for Narcolepsy, Palo Alto, CA; and Department of Pharmacology (Dr. Sakurai), Institute of Basic Medical Sciences, University of Tsukuba, Japan.


* To whom correspondence should be addressed. E-mail: tscammel{at}bidmc.harvard.edu.

Abstract-- Background: 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. Objective: To examine whether other markers of the orexin neurons are lost in narcolepsy with cataplexy. Methods: 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. Results: 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. Conclusions: 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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