Concomitant loss of dynorphin, NARP, and orexin in narcolepsy.

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.

• Authors: A Crocker, R A España, M Papadopoulou, C B Saper, J Faraco, T Sakurai, M Honda, E Mignot, T E Scammell
• Journal: Neurology (Neurology) Vol. 65 Issue 8 Pg. 1184-8 (Oct 25 2005) ISSN: 1526-632X [Electronic] United States
• PMID: 16247044 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Autoantibodies
• Intracellular Signaling Peptides and Proteins
• Nerve Tissue Proteins
• Neuropeptides
• Orexins
• RNA, Messenger
• neuronal pentraxin
• Dynorphins
• C-Reactive Protein

Topics

• Aged
• Autoantibodies (immunology)
• Autoimmune Diseases of the Nervous System (complications, pathology, physiopathology)
• Brain Mapping
• C-Reactive Protein (deficiency, genetics, immunology)
• Dynorphins (deficiency, genetics, immunology)
• Humans
• Hypothalamus (metabolism, pathology, physiopathology)
• Immunohistochemistry
• Intracellular Signaling Peptides and Proteins (deficiency, genetics, immunology)
• Male
• Middle Aged
• Narcolepsy (etiology, pathology, physiopathology)
• Nerve Degeneration (genetics, pathology, physiopathology)
• Nerve Tissue Proteins (deficiency, genetics, immunology)
• Neural Pathways (metabolism, pathology, physiopathology)
• Neurodegenerative Diseases (complications, pathology, physiopathology)
• Neurons (metabolism, pathology)
• Neuropeptides (deficiency, genetics, immunology)
• Orexins
• RNA, Messenger (metabolism)