Narp immunostaining of human hypocretin (orexin) neurons: loss in narcolepsy.
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.
Blouin
A M
AM
Department of Psychiatry, Brain Research Institute, University of California, Los Angeles, CA, USA.
Thannickal
T C
TC
Worley
P F
PF
Baraban
J M
JM
Reti
I M
IM
Siegel
J M
JM
D001931:Brain Mapping; D002097:C-Reactive Protein / Q000172:deficiency; D006801:Humans; D007026:Hypothalamic Area, Lateral / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007031:Hypothalamus / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D007034:Hypothalamus, Posterior / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency*; D009290:Narcolepsy / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D009419:Nerve Tissue Proteins / Q000172:deficiency; D009434:Neural Pathways / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D019636:Neurodegenerative Diseases / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D009479:Neuropeptides / Q000172:deficiency*; D000068797:Orexins; D012890:Sleep / Q000502:physiology; D000099153:Pentraxins
D002097:C-Reactive Protein; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D000068797:Orexins; D000099153:Pentraxins