Distinct narcolepsy syndromes in Orexin receptor-2 and Orexin null mice: molecular genetic dissection of Non-REM and REM sleep regulatory processes

Research output: Contribution to journal › Journal article › Research › peer-review

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Distinct narcolepsy syndromes in Orexin receptor-2 and Orexin null mice : molecular genetic dissection of Non-REM and REM sleep regulatory processes. / Willie, Jon T; Chemelli, Richard M; Sinton, Christopher M; Tokita, Shigeru; Williams, S Clay; Kisanuki, Yaz Y; Marcus, Jacob N; Lee, Charlotte; Elmquist, Joel K; Kohlmeier, Kristi Anne; Leonard, Christopher S; Richardson, James A; Hammer, Robert E; Yanagisawa, Masashi.

In: Neuron, Vol. 38, No. 5, 2003, p. 715-30.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Willie, JT, Chemelli, RM, Sinton, CM, Tokita, S, Williams, SC, Kisanuki, YY, Marcus, JN, Lee, C, Elmquist, JK, Kohlmeier, KA, Leonard, CS, Richardson, JA, Hammer, RE & Yanagisawa, M 2003, 'Distinct narcolepsy syndromes in Orexin receptor-2 and Orexin null mice: molecular genetic dissection of Non-REM and REM sleep regulatory processes', Neuron, vol. 38, no. 5, pp. 715-30.

APA

Willie, J. T., Chemelli, R. M., Sinton, C. M., Tokita, S., Williams, S. C., Kisanuki, Y. Y., Marcus, J. N., Lee, C., Elmquist, J. K., Kohlmeier, K. A., Leonard, C. S., Richardson, J. A., Hammer, R. E., & Yanagisawa, M. (2003). Distinct narcolepsy syndromes in Orexin receptor-2 and Orexin null mice: molecular genetic dissection of Non-REM and REM sleep regulatory processes. Neuron, 38(5), 715-30.

Vancouver

Willie JT, Chemelli RM, Sinton CM, Tokita S, Williams SC, Kisanuki YY et al. Distinct narcolepsy syndromes in Orexin receptor-2 and Orexin null mice: molecular genetic dissection of Non-REM and REM sleep regulatory processes. Neuron. 2003;38(5):715-30.

Author

Willie, Jon T ; Chemelli, Richard M ; Sinton, Christopher M ; Tokita, Shigeru ; Williams, S Clay ; Kisanuki, Yaz Y ; Marcus, Jacob N ; Lee, Charlotte ; Elmquist, Joel K ; Kohlmeier, Kristi Anne ; Leonard, Christopher S ; Richardson, James A ; Hammer, Robert E ; Yanagisawa, Masashi. / Distinct narcolepsy syndromes in Orexin receptor-2 and Orexin null mice : molecular genetic dissection of Non-REM and REM sleep regulatory processes. In: Neuron. 2003 ; Vol. 38, No. 5. pp. 715-30.

Bibtex

@article{593c89384b0949c1b844f6de591be818,
title = "Distinct narcolepsy syndromes in Orexin receptor-2 and Orexin null mice: molecular genetic dissection of Non-REM and REM sleep regulatory processes",
abstract = "Narcolepsy-cataplexy, a neurological disorder associated with the absence of hypothalamic orexin (hypocretin) neuropeptides, consists of two underlying problems: inability to maintain wakefulness and intrusion of rapid eye movement (REM) sleep into wakefulness. Here we document, using behavioral, electrophysiological, and pharmacological criteria, two distinct classes of behavioral arrests exhibited by mice deficient in orexin-mediated signaling. Both OX2R(-/-) and orexin(-/-) mice are similarly affected with behaviorally abnormal attacks of non-REM sleep ({"}sleep attacks{"}) and show similar degrees of disrupted wakefulness. In contrast, OX2R(-/-) mice are only mildly affected with cataplexy-like attacks of REM sleep, whereas orexin(-/-) mice are severely affected. Absence of OX2Rs eliminates orexin-evoked excitation of histaminergic neurons in the hypothalamus, which gate non-REM sleep onset. While normal regulation of wake/non-REM sleep transitions depends critically upon OX2R activation, the profound dysregulation of REM sleep control unique to the narcolepsy-cataplexy syndrome emerges from loss of signaling through both OX2R-dependent and OX2R-independent pathways.",
keywords = "Animals, Arousal, Carrier Proteins, Cells, Cultured, Clomipramine, Disease Models, Animal, Efferent Pathways, Electroencephalography, Electromyography, Histamine, Hypothalamic Area, Lateral, Hypothalamus, Intracellular Signaling Peptides and Proteins, Male, Mice, Mice, Knockout, Narcolepsy, Neuropeptides, Receptors, G-Protein-Coupled, Receptors, Neuropeptide, Sleep, Sleep, REM, Synaptic Transmission",
author = "Willie, {Jon T} and Chemelli, {Richard M} and Sinton, {Christopher M} and Shigeru Tokita and Williams, {S Clay} and Kisanuki, {Yaz Y} and Marcus, {Jacob N} and Charlotte Lee and Elmquist, {Joel K} and Kohlmeier, {Kristi Anne} and Leonard, {Christopher S} and Richardson, {James A} and Hammer, {Robert E} and Masashi Yanagisawa",
year = "2003",
language = "English",
volume = "38",
pages = "715--30",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "5",

}

RIS

TY - JOUR

T1 - Distinct narcolepsy syndromes in Orexin receptor-2 and Orexin null mice

T2 - molecular genetic dissection of Non-REM and REM sleep regulatory processes

AU - Willie, Jon T

AU - Chemelli, Richard M

AU - Sinton, Christopher M

AU - Tokita, Shigeru

AU - Williams, S Clay

AU - Kisanuki, Yaz Y

AU - Marcus, Jacob N

AU - Lee, Charlotte

AU - Elmquist, Joel K

AU - Kohlmeier, Kristi Anne

AU - Leonard, Christopher S

AU - Richardson, James A

AU - Hammer, Robert E

AU - Yanagisawa, Masashi

PY - 2003

Y1 - 2003

N2 - Narcolepsy-cataplexy, a neurological disorder associated with the absence of hypothalamic orexin (hypocretin) neuropeptides, consists of two underlying problems: inability to maintain wakefulness and intrusion of rapid eye movement (REM) sleep into wakefulness. Here we document, using behavioral, electrophysiological, and pharmacological criteria, two distinct classes of behavioral arrests exhibited by mice deficient in orexin-mediated signaling. Both OX2R(-/-) and orexin(-/-) mice are similarly affected with behaviorally abnormal attacks of non-REM sleep ("sleep attacks") and show similar degrees of disrupted wakefulness. In contrast, OX2R(-/-) mice are only mildly affected with cataplexy-like attacks of REM sleep, whereas orexin(-/-) mice are severely affected. Absence of OX2Rs eliminates orexin-evoked excitation of histaminergic neurons in the hypothalamus, which gate non-REM sleep onset. While normal regulation of wake/non-REM sleep transitions depends critically upon OX2R activation, the profound dysregulation of REM sleep control unique to the narcolepsy-cataplexy syndrome emerges from loss of signaling through both OX2R-dependent and OX2R-independent pathways.

AB - Narcolepsy-cataplexy, a neurological disorder associated with the absence of hypothalamic orexin (hypocretin) neuropeptides, consists of two underlying problems: inability to maintain wakefulness and intrusion of rapid eye movement (REM) sleep into wakefulness. Here we document, using behavioral, electrophysiological, and pharmacological criteria, two distinct classes of behavioral arrests exhibited by mice deficient in orexin-mediated signaling. Both OX2R(-/-) and orexin(-/-) mice are similarly affected with behaviorally abnormal attacks of non-REM sleep ("sleep attacks") and show similar degrees of disrupted wakefulness. In contrast, OX2R(-/-) mice are only mildly affected with cataplexy-like attacks of REM sleep, whereas orexin(-/-) mice are severely affected. Absence of OX2Rs eliminates orexin-evoked excitation of histaminergic neurons in the hypothalamus, which gate non-REM sleep onset. While normal regulation of wake/non-REM sleep transitions depends critically upon OX2R activation, the profound dysregulation of REM sleep control unique to the narcolepsy-cataplexy syndrome emerges from loss of signaling through both OX2R-dependent and OX2R-independent pathways.

KW - Animals

KW - Arousal

KW - Carrier Proteins

KW - Cells, Cultured

KW - Clomipramine

KW - Disease Models, Animal

KW - Efferent Pathways

KW - Electroencephalography

KW - Electromyography

KW - Histamine

KW - Hypothalamic Area, Lateral

KW - Hypothalamus

KW - Intracellular Signaling Peptides and Proteins

KW - Male

KW - Mice

KW - Mice, Knockout

KW - Narcolepsy

KW - Neuropeptides

KW - Receptors, G-Protein-Coupled

KW - Receptors, Neuropeptide

KW - Sleep

KW - Sleep, REM

KW - Synaptic Transmission

M3 - Journal article

C2 - 12797957

VL - 38

SP - 715

EP - 730

JO - Neuron

JF - Neuron

SN - 0896-6273

IS - 5

ER -

ID: 38346557