Hypocretin (orexin) biology and the pathophysiology of narcolepsy with cataplexy

  title={Hypocretin (orexin) biology and the pathophysiology of narcolepsy with cataplexy},
  author={Roland S. Liblau and Anne Vassalli and Ali Seifinejad and Mehdi Tafti},
  journal={The Lancet Neurology},

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Mapping the Hypocretin/Orexin Neuronal System: An Unexpectedly Productive Journey

This paper has had a surprisingly broad impact on neuroscience research, particularly since it was originally rejected by the Journal of Neuroscience, but the citation rate of this paper underscores the critical nature of such basic research.

CD4+ T-Cell Reactivity to Orexin/Hypocretin in Patients With Narcolepsy Type 1

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Narcolepsy: pathophysiology and pharmacology.

  • S. Nishino
  • Psychology, Medicine
    The Journal of clinical psychiatry
  • 2007
The major pathophysiology of human narcolepsy has recently been revealed by the extension of discoveries of nar colepsy genes in animal models, and hypocretin/orexin ligand deficiency has been shown in about 90% of humanNarcoleptic-cataplexy.

Elevated Tribbles homolog 2-specific antibody levels in narcolepsy patients.

Evidence is provided that reactive autoantibodies in human narcolepsy are an autoimmune disorder, provided by ELISA analysis of Serum of a patient showed specific immunoreactivity with over 86% of hypocretin neurons in the mouse hypothalamus.

Orexin neurons suppress narcolepsy via 2 distinct efferent pathways.

It is suggested that DR serotonergic and LC noradrenergic neurons play differential roles in orexin neuron-dependent regulation of sleep/wakefulness and highlight a pharmacogenetic approach for the amelioration of narcolepsy.

Hypothalamic immunopathology in anti-Ma-associated diencephalitis with narcolepsy-cataplexy.

The encephalitic process, responsible for narcolepsy-cataplexy and hypoc retin deficiency, reflects a CD8+ inflammatory-mediated response against hypocretin neurons.

Pattern of Hypocretin (Orexin) Soma and Axon Loss, and Gliosis, in Human Narcolepsy

It is reported that the percentage loss of Hcrt cells and percentage elevation of GFAP staining are variable across forebrain and brainstem nuclei, and are maximal in the posterior and tuberomammillary hypothalamic region, consistent with the hypotheses that the loss of hypocretin function in narcolepsy results from a cytotoxic or immunologically mediated attack focused on hypocrretin receptor 2.

Post-H1N1 narcolepsy-cataplexy.

The cause of narcolepsy is likely autoimmune based on the HLA association, association with T-cell receptor polymorphisms, and recently reported Tribbles 2 autoantibodies, and twin pairs are most often discordant (65% to 80%), and environmental triggers are suspected to play a critical role.

Dopaminergic regulation of sleep and cataplexy in a murine model of narcolepsy.

A role for the dopamine system in regulating sleep attacks and cataplexy in a murine model of narcolepsy is shown and it is found that catapLexy is modulated by a D2-like receptor mechanism, whereas dopamine modulates sleep attacks by aD1-like receptors mechanism.