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Concomitant loss of dynorphin, NARP, and orexin in narcolepsy

A Crocker1, R A España, M Papadopoulou

  • 1Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.

Neurology
|October 26, 2005
PubMed
Abstract

Insights

Narcolepsy with cataplexy involves the loss of orexin-producing neurons. This study found that markers like prodynorphin and neuronal activity-regulated pentraxin (NARP) are also significantly reduced in narcolepsy patients.

Area of Science:

  • Neuroscience
  • Sleep Medicine

Background:

  • Narcolepsy with cataplexy is linked to orexin/hypocretin deficiency.
  • The exact cause is debated, with theories including autoimmune destruction or functional failure of orexin neurons.

Purpose of the Study:

  • To investigate the loss of other orexin neuron markers in narcolepsy with cataplexy.
  • To determine if neuronal activity-regulated pentraxin (NARP) and prodynorphin are affected.

Main Methods:

  • Immunohistochemistry and in situ hybridization were employed.
  • Hypothalami from control and narcolepsy patients were analyzed for orexin, NARP, and prodynorphin expression.

Main Results:

  • In controls, over 80% of orexin neurons expressed prodynorphin mRNA and NARP.
  • Narcolepsy patients showed a drastic reduction, with only 5-10% of normal levels for these markers.

Conclusions:

  • The findings strongly suggest a loss of orexin-producing neurons in narcolepsy with cataplexy.
  • Reduced dynorphin and NARP may also play a role in narcolepsy symptoms.

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