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Published online before print August 31, 2005, doi:10.1212/01.wnl.0000175219.01544.c8)
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Received December 23, 2004
Accepted June 2, 2005

Narp immunostaining of human hypocretin (orexin) neurons: Loss in narcolepsy

A. M. Blouin BS, T. C. Thannickal PhD, P. F. Worley MD, J. M. Baraban MD, PhD, I. M. Reti MD, and J. M. Siegel PhD*

From the Department of Psychiatry and Brain Research Institute (A.M. Blouin, Dr. Thannickal, and Dr. Siegel), University of California, Los Angeles, CA; the Neurobiology Research (A.M. Blouin, Dr. Thannickal, and Dr. Siegel), VA Greater Los Angeles Healthcare System, North Hills, CA; and the Departments of Neuroscience (Drs. Worley and Baraban), Neurology (Dr. Worley), and Psychiatry and Behavioral Sciences (Dr. Baraban and Reti), Johns Hopkins University School of Medicine, Baltimore, MD.


* To whom correspondence should be addressed. E-mail: jsiegel{at}ucla.edu.

Abstract-- Objective: To investigate whether neuronal activity-regulated pentraxin (Narp) colocalizes with hypocretin (Hcrt or orexin) in the normal human brain and to determine if Narp staining is lost in the narcoleptic human brain. Background: Human narcolepsy is characterized by a loss of the peptide hypocretin in the hypothalamus. This loss could result from the degeneration of neurons containing hypocretin or from a more specific loss of the ability of these neurons to synthesize Hcrt. Narp has been found to colocalize with hypocretin in the rat hypothalamus. Methods: We investigated the distribution of Narp in three normal and four narcoleptic human postmortem brains using immunohistochemistry with an antibody to Narp. Colocalization studies of Narp and hypocretin were also performed in two normal brains using immunohistochemistry with an antibody to Narp and an antibody to hypocretin. Results: We found that Narp colocalizes with hypocretin in the lateral hypothalamic area (LHA), the dorsomedial hypothalamus (DMH), the dorsal hypothalamic area (DHA), and the posterior hypothalamic area (PHA) of the normal human. The number of Narp-positive neurons was reduced by 89% in these areas of the narcoleptic hypothalamus. In contrast, Narp staining in the paraventricular (Pa) and supraoptic nuclei (SO) of the human hypothalamus did not differ between normal and narcoleptic brains. Conclusions: This finding supports the hypothesis that narcolepsy results from the specific loss of hypocretin neurons. Loss of hypothalamic Narp may contribute to the symptoms of narcolepsy.




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