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Narcolepsy and Orexin/Hypocretin

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Sleep and its Disorders

Part of the book series: Translational Medicine Research ((TRAMERE))

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Abstract

Narcolepsy is characterized by excessive daytime sleepiness, cataplexy, sleep paralysis, hypnagogic and hypnopompic hallucination, and disturbed nocturnal sleep. A deficient endogenous orexin system due to neuronal loss of orexin neurons in the hypothalamus is the main pathophysiological mechanism for narcolepsy in humans. Recent advances have shown the value of finding decreased cerebrospinal fluid orexin in the diagnosis of human narcolepsy, and the role of the human leucocyte antigen (HLA) gene in the pathogenesis of narcolepsy. Also, there is information on the association between respiratory regulation and the orexin system. Animal models have been used in the pharmacologic study of narcolepsy. Knowledge of how therapeutic agents used to treat narcolepsy act and the underlying neuronal mechanisms come from studies in animal models. Orexin replacement is likely to be a future treatment option for orexin-deficient narcolepsy patients. In this chapter, we will discuss the biology of the orexin system, the clinical aspects of narcolepsy, and examples of translation from basic science research into clinical practice in the field of narcolepsy.

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Abbreviations

BST:

Bed nucleus of the stria terminalis

CSF:

Cerebrospinal fluid

DAT:

Dopaminergic transporter

DMN:

Dorsal medial hypothalamic nucleus

DR:

Dorsal raphe

EDS:

Excessive daytime sleepiness

GHB:

Gamma-hydroxybutyrate

HLA:

Human leukocyte antigen

LC:

Locus coeruleus

LDT:

Laterodorsal tegmental nucleus

MAOI:

Monoamine oxidase inhibitor

Orx1:

Orexin-1

Orx2:

Orexin-2

OSAHS:

Obstructive sleep apnea-hypopnea syndrome

PPT:

Pedunculopontine nucleus

SNRI:

Serotonin norepinephrine reuptake inhibitor

SSRI:

Selective serotonin reuptake inhibitor

TCA:

Tricyclic antidepressant

TMN:

Tuberomammillary nucleus

VLPO:

Ventrolateral preoptic nucleus

VTA:

Ventral tegmental area

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Authors and Affiliations

  1. Department of Respiratory Medicine, Peking University People’s Hospital, Beijing, China

    Fu Long Xiao & Fang Han

  2. Department of Neurology, Peking University People’s Hospital, Beijing, China

    Jun Zhang

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  1. John Miclot Professor, Division of Sleep Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Allan I. Pack

  2. Department of Pulmonary and Critical Care Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China

    Qing Yun Li

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Xiao, F.L., Zhang, J., Han, F. (2022). Narcolepsy and Orexin/Hypocretin. In: Pack, A.I., Li, Q.Y. (eds) Sleep and its Disorders. Translational Medicine Research. Springer, Dordrecht. https://doi.org/10.1007/978-94-024-2168-2_12

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