The neurobiological basis of narcolepsy

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The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity

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Neurons containing hypocretin (orexin) project to multiple neuronal systems

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Narcolepsy in orexin Knockout Mice

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Hypothalamic regulation of sleep and circadian rhythms

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The Sleep Disorder Canine Narcolepsy Is Caused by a Mutation in the Hypocretin (Orexin) Receptor 2 Gene

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A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains

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Reduced Number of Hypocretin Neurons in Human Narcolepsy

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Hypocretin (orexin) deficiency in human narcolepsy

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Genetic Ablation of Orexin Neurons in Mice Results in Narcolepsy, Hypophagia, and Obesity

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Neural substrates of awakening probed with optogenetic control of hypocretin neurons

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A putative flip–flop switch for control of REM sleep

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Practice Parameters for Clinical Use of the Multiple Sleep Latency Test and the Maintenance of Wakefulness Test

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The role of cerebrospinal fluid hypocretin measurement in the diagnosis of narcolepsy and other hypersomnias

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Tuning arousal with optogenetic modulation of locus coeruleus neurons

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Discharge of Identified Orexin/Hypocretin Neurons across the Sleep-Waking Cycle

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Behavioral Correlates of Activity in Identified Hypocretin/Orexin Neurons

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Mechanisms of impaired regulation by CD4+CD25+FOXP3+ regulatory T cells in human autoimmune diseases

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Fos Expression in Orexin Neurons Varies with Behavioral State

Estabrooke, I. V., McCarthy, M. T., Ko, E., Chou, T. C., Chemelli, R. M., Yanagisawa, M., Saper, C. B., & Scammell, T. E. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-05-01656.2001 · Cited by 654 · see citing works

Distinct Narcolepsy Syndromes in Orexin Receptor-2 and Orexin Null Mice

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., et al. (2003) · Neuron · doi:10.1016/s0896-6273(03)00330-1 · Cited by 645 · see citing works

The significance of OX40 and OX40L to T‐cell biology and immune disease

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Complex HLA-DR and -DQ Interactions Confer Risk of Narcolepsy-Cataplexy in Three Ethnic Groups

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Critical role of dorsomedial hypothalamic nucleus in a wide range of behavioral circadian rhythms

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Afferents to the orexin neurons of the rat brain

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Arousal and reward: a dichotomy in orexin function

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Hypothalamic Hypocretin (Orexin): Robust Innervation of the Spinal Cord

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Direct Involvement of Orexinergic Systems in the Activation of the Mesolimbic Dopamine Pathway and Related Behaviors Induced by Morphine

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Narcolepsy onset is seasonal and increased following the 2009 H1N1 pandemic in china

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Narcolepsy

Scammell, T. E. (2015) · New England Journal of Medicine · doi:10.1056/nejmra1500587 · Cited by 506 · see citing works

Narcolepsy is strongly associated with the T-cell receptor alpha locus

Hallmayer, J. F., Faraco, J. H., Lin, L., Hesselson, S., Winkelmann, J., Kawashima, M., Mayer, G., Plazzi, G., Nevšímalová, S., Bourgin, P., et al. (2009) · Nature Genetics · doi:10.1038/ng.372 · Cited by 478 · see citing works

Hypocretin/Orexin Excites Hypocretin Neurons via a Local Glutamate Neuron—A Potential Mechanism for Orchestrating the Hypothalamic Arousal System

Li, Y., Gao, X., Sakurai, T., & van den Pol, A. N. (2002) · Neuron · doi:10.1016/s0896-6273(02)01132-7 · Cited by 476 · see citing works

Indexed Pain Journals

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Input of Orexin/Hypocretin Neurons Revealed by a Genetically Encoded Tracer in Mice

Sakurai, T., Nagata, R., Yamanaka, A., Kawamura, H., Tsujino, N., Muraki, Y., Kageyama, H., Kunita, S., Takahashi, S., Goto, K., et al. (2005) · Neuron · doi:10.1016/j.neuron.2005.03.010 · Cited by 468 · see citing works

Low cerebrospinal fluid hypocretin (orexin) and altered energy homeostasis in human narcolepsy

Nishino, S., Ripley, B. A., Overeem, S., Nevšímalová, S., Lammers, G. J., Vaňková, J., Okun, M. L., Rogers, W. M., Brooks, S. N., & Mignot, E. J.-M. (2001) · Annals of Neurology · doi:10.1002/ana.1130 · Cited by 451 · see citing works

Sympathetic and cardiovascular actions of orexins in conscious rats

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Orexin (Hypocretin) Neurons Contain Dynorphin

Chou, T. C., Lee, C. E., Lü, J., Elmquist, J. K., Hara, J., Willie, J. T., Beuckmann, C. T., Chemelli, R. M., Sakurai, T., Yanagisawa, M., et al. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-19-j0003.2001 · Cited by 430 · see citing works

The Epidemiology of Narcolepsy in Olmsted County, Minnesota: A Population-Based Study

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Increased Incidence and Clinical Picture of Childhood Narcolepsy following the 2009 H1N1 Pandemic Vaccination Campaign in Finland

Partinen, M., Saarenpää‐Heikkilä, O., Ilveskoski, I., Hublin, C., Linna, M., Olsén, P., Nokelainen, P. T., Alén, R., Wallden, T., Espo, M., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0033723 · Cited by 406 · see citing works

Behavioral State Instability in Orexin Knock-Out Mice

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HLA DQB1*0602 is Associated With Cataplexy in 509 Narcoleptic Patients

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Involvement of the lateral hypothalamic peptide orexin in morphine dependence and withdrawal

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Elevated Anti-Streptococcal Antibodies in Patients with Recent Narcolepsy Onset

Aran, A. A., Lin, L., Nevšímalová, S., Plazzi, G., Hong, S., Weiner, K., Zeitzer, J. M., & Mignot, E. J.-M. (2009) · SLEEP · doi:10.1093/sleep/32.8.979 · Cited by 352 · see citing works

Orexin peptides prevent cataplexy and improve wakefulness in an orexin neuron-ablated model of narcolepsy in mice

Mieda, M., Willie, J. T., Hara, J., Sinton, C. M., Sakurai, T., & Yanagisawa, M. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0400590101 · Cited by 341 · see citing works

T cells in patients with narcolepsy target self-antigens of hypocretin neurons

Latorre, D., Kallweit, U., Armentani, E., Foglierini, M., Mele, F., Cassotta, A., Jovic, S., Jarrossay, D., Mathis, J., Zellini, F., et al. (2018) · Nature · doi:10.1038/s41586-018-0540-1 · Cited by 334 · see citing works

Increased body-mass index in patients with narcolepsy

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Role of lateral hypothalamic orexin neurons in reward processing and addiction

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Independent Feeding and Metabolic Actions of Orexins in Mice

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Orexin receptor antagonism for treatment of insomnia

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Narp regulates homeostatic scaling of excitatory synapses on parvalbumin-expressing interneurons

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Wake-promoting and sleep-suppressing actions of hypocretin (orexin): basal forebrain sites of action

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Elevated Tribbles homolog 2–specific antibody levels in narcolepsy patients

Cvetkovic-Lopes, V., Bayer, L., Dorsaz, S., Maret, S., Pradervand, S., Dauvilliers, Y. A., Lecendreux, M., Lammers, G. J., Donjacour, C. E. H. M., Pasquier, R. D., et al. (2010) · Journal of Clinical Investigation · doi:10.1172/jci41366 · Cited by 306 · see citing works

Concomitant loss of dynorphin, NARP, and orexin in narcolepsy

Crocker, A., España, R. A., Papadopoulou, M., Saper, C. B., Faraco, J., Sakurai, T., Honda, M., Mignot, E., & Scammell, T. E. (2005) · Neurology · doi:10.1212/01.wnl.0000168173.71940.ab · Cited by 301 · see citing works

Mechanism for Hypocretin-mediated sleep-to-wake transitions

Carter, M. E., Brill, J., Bonnavion, P., Huguenard, J. R., Huerta, R., & de Lecea, L. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1202526109 · Cited by 274 · see citing works

Differential Roles of Orexin Receptor-1 and -2 in the Regulation of Non-REM and REM Sleep

Mieda, M., Hasegawa, E., Kisanuki, Y. Y., Sinton, C. M., Yanagisawa, M., & Sakurai, T. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.6506-10.2011 · Cited by 268 · see citing works

Localized Loss of Hypocretin (Orexin) Cells in Narcolepsy Without Cataplexy

Thannickal, T. C., Nienhuis, R., & Siegel, J. M. (2009) · SLEEP · doi:10.1093/sleep/32.8.993 · Cited by 267 · see citing works

Localization of the Brainstem GABAergic Neurons Controlling Paradoxical (REM) Sleep

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The role of antigen presenting cells in multiple sclerosis

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Hypocretin (orexin) facilitates reward by attenuating the antireward effects of its cotransmitter dynorphin in ventral tegmental area

Muschamp, J. W., Hollander, J. A., Thompson, J. L., Voren, G., Hassinger, L. C., Onvani, S., Kamenecka, T. M., Borgland, S. L., Kenny, P. J., & Carlezon, W. A. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1315542111 · Cited by 250 · see citing works

Pharmacogenetic Modulation of Orexin Neurons Alters Sleep/Wakefulness States in Mice

Sasaki, K., Suzuki, M., Mieda, M., Tsujino, N., Roth, B. L., & Sakurai, T. (2011) · PLoS ONE · doi:10.1371/journal.pone.0020360 · Cited by 249 · see citing works

ImmunoChip Study Implicates Antigen Presentation to T Cells in Narcolepsy

Faraco, J. H., Lin, L., Kornum, B. R., Kenny, E. E., Trynka, G., Einen, M. A., Rico, T., Lichtner, P., Dauvilliers, Y. A., Arnulf, I., et al. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003270 · Cited by 244 · see citing works

Antibodies to influenza nucleoprotein cross-react with human hypocretin receptor 2

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Cataplexy-Active Neurons in the Hypothalamus

John, J., Wu, M., Boehmer, L. N., & Siegel, J. M. (2004) · Neuron · doi:10.1016/s0896-6273(04)00247-8 · Cited by 227 · see citing works

Predictors of Hypocretin (Orexin) Deficiency in Narcolepsy Without Cataplexy

Andlauer, O., Moore, H. E., Hong, S., Dauvilliers, Y. A., Kanbayashi, T., Nishino, S., Han, F., Silber, M. H., Rico, T., Einen, M. A., et al. (2012) · SLEEP · doi:10.5665/sleep.2080 · Cited by 222 · see citing works

Clinical, polysomnographic and genome‐wide association analyses of narcolepsy with cataplexy: a European Narcolepsy Network study

Luca, G., Haba‐Rubio, J., Dauvilliers, Y. A., Lammers, G. J., Overeem, S., Donjacour, C. E. H. M., Mayer, G., Javidi, S., Iranzo, Á., Santamaría, J., et al. (2013) · Journal of Sleep Research · doi:10.1111/jsr.12044 · Cited by 221 · see citing works

Conditional Ablation of Orexin/Hypocretin Neurons: A New Mouse Model for the Study of Narcolepsy and Orexin System Function

Tabuchi, S., Tsunematsu, T., Black, S. W., Tominaga, M., Maruyama, M., Takagi, K., Minokoshi, Y., Sakurai, T., Kilduff, T. S., & Yamanaka, A. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.0073-14.2014 · Cited by 216 · see citing works

Paradoxical (REM) sleep genesis: The switch from an aminergic–cholinergic to a GABAergic–glutamatergic hypothesis

Luppi, P., Gervasoni, D., Verret, L., Goutagny, R., Peyron, C., Salvert, D., Léger, L., & Fort, P. (2006) · Journal of Physiology-Paris · doi:10.1016/j.jphysparis.2007.05.006 · Cited by 214 · see citing works

Incidence of narcolepsy after H1N1 influenza and vaccinations: Systematic review and meta-analysis

Sarkanen, T., Alakuijala, A., Dauvilliers, Y. A., & Partinen, M. (2017) · Sleep Medicine Reviews · doi:10.1016/j.smrv.2017.06.006 · Cited by 206 · see citing works

DQB1 Locus Alone Explains Most of the Risk and Protection in Narcolepsy with Cataplexy in Europe

Behalf of the European Narcolepsy Network (EU-NN), Tafti, M., Hor, H., Dauvilliers, Y. A., Lammers, G. J., Overeem, S., Mayer, G., Javidi, S., Iranzo, Á., Santamaría, J., et al. (2014) · SLEEP · doi:10.5665/sleep.3300 · Cited by 202 · see citing works

Complex movement disorders at disease onset in childhood narcolepsy with cataplexy

Plazzi, G., Pizza, F., Palaia, V., Franceschini, C., Poli, F., Moghadam, K. K., Cortelli, P., Nobili, L., Bruni, O., Dauvilliers, Y. A., et al. (2011) · Brain · doi:10.1093/brain/awr244 · Cited by 201 · see citing works

Difference in obesity phenotype between orexin-knockout mice and orexin neuron-deficient mice with same genetic background and environmental conditions

Hara, J., Yanagisawa, M., & Sakurai, T. (2005) · Neuroscience Letters · doi:10.1016/j.neulet.2005.01.046 · Cited by 198 · see citing works

Awake dynamics and brain-wide direct inputs of hypothalamic MCH and orexin networks

González, J. A., Ιορδανίδου, Π., Strom, M., Adamantidis, A., & Burdakov, D. (2016) · Nature Communications · doi:10.1038/ncomms11395 · Cited by 193 · see citing works

Clinical Aspects of Narcolepsy-Cataplexy Across Ethnic Groups

Okun, M. L., Lin, L., Pelin, Z., Hong, S.-C., & Mignot, E. J.-M. (2002) · SLEEP · doi:10.1093/sleep/25.1.27 · Cited by 192 · see citing works

Coreleased Orexin and Glutamate Evoke Nonredundant Spike Outputs and Computations in Histamine Neurons

Schöne, C., Apergis‐Schoute, J., Sakurai, T., Adamantidis, A., & Burdakov, D. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.03.055 · Cited by 190 · see citing works

Genome-wide association study identifies new HLA class II haplotypes strongly protective against narcolepsy

Hor, H., Kutalik, Z., Dauvilliers, Y. A., Valsesia, A., Lammers, G. J., Donjacour, C. E. H. M., Iranzo, Á., Santamaría, J., Peraita‐Adrados, R., Vicario, J. L., et al. (2010) · Nature Genetics · doi:10.1038/ng.647 · Cited by 189 · see citing works

Autoimmunity to hypocretin and molecular mimicry to flu in type 1 narcolepsy

Luo, G., Ambati, A., Lin, L., Bonvalet, M., Partinen, M., Ji, X., Maecker, H. T., & Mignot, E. J.-M. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1818150116 · Cited by 188 · see citing works

The autoimmune basis of narcolepsy

Mahlios, J., la Herrán-Arita, A. K. D., & Mignot, E. J.-M. (2013) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2013.04.013 · Cited by 179 · see citing works

Nocturnal Rapid Eye Movement Sleep Latency for Identifying Patients With Narcolepsy/Hypocretin Deficiency

Andlauer, O., Moore, H. E., Jouhier, L., Drake, C. L., Peppard, P. E., Han, F., Hong, S., Poli, F., Plazzi, G., O'Hara, R. M., et al. (2013) · JAMA Neurology · doi:10.1001/jamaneurol.2013.1589 · Cited by 177 · see citing works

Narp immunostaining of human hypocretin (orexin) neurons: Loss in narcolepsy

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Hypocretin Levels in Sporadic and Familial Cases of Canine Narcolepsy

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Orexin neurons suppress narcolepsy via 2 distinct efferent pathways

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HLA-DPB1 and HLA Class I Confer Risk of and Protection from Narcolepsy

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Orexin Mediates the Expression of Precipitated Morphine Withdrawal and Concurrent Activation of the Nucleus Accumbens Shell

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Structure and ligand-binding mechanism of the human OX1 and OX2 orexin receptors

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Nonpeptide orexin type-2 receptor agonist ameliorates narcolepsy-cataplexy symptoms in mouse models

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Brainstem mechanisms of paradoxical (REM) sleep generation

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Orexin receptor 2 expression in the posterior hypothalamus rescues sleepiness in narcoleptic mice

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A Hypothalamic Switch for REM and Non-REM Sleep

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Rapid eye movement sleep behaviour disorder in patients with narcolepsy is associated with hypocretin-1 deficiency

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Projection-Target-Defined Effects of Orexin and Dynorphin on VTA Dopamine Neurons

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Abnormal Sleep/Wake Dynamics in Orexin Knockout Mice

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Eating Disorder and Metabolism in Narcoleptic Patients

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Efferent projections from the median preoptic nucleus to sleep- and arousal-regulatory nuclei in the rat brain

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Greatly increased numbers of histamine cells in human narcolepsy with cataplexy

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Spontaneous Food Choice in Narcolepsy

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Orexin Directly Excites Orexin Neurons through Orexin 2 Receptor

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Neurochemical Heterogeneity Among Lateral Hypothalamic Hypocretin/Orexin and Melanin-Concentrating Hormone Neurons Identified Through Single-Cell Gene Expression Analysis

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Orexin Neurons Are Necessary for the Circadian Control of REM Sleep

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Role of the Medial Prefrontal Cortex in Cataplexy

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Serotonin neurons in the dorsal raphe mediate the anticataplectic action of orexin neurons by reducing amygdala activity

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Comprehensive Behavioral Analysis of Male Ox1r−/− Mice Showed Implication of Orexin Receptor-1 in Mood, Anxiety, and Social Behavior

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Depressive feelings in children with narcolepsy

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Increased Heart Rate Variability but Normal Resting Metabolic Rate in Hypocretin/Orexin-Deficient Human Narcolepsy

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Hypocretin-2 Saporin Lesions of the Ventrolateral Periaquaductal Gray (vlPAG) Increase REM Sleep in Hypocretin Knockout Mice

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Narcolepsy-Associated HLA Class I Alleles Implicate Cell-Mediated Cytotoxicity

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Narcolepsy patients have antibodies that stain distinct cell populations in rat brain and influence sleep patterns

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The role of orexin in Alzheimer disease: From sleep-wake disturbance to therapeutic target

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To sleep or not to sleep – Effects on memory in normal aging and disease

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Targeting the Orexin System in the Pharmacological Management of Insomnia and Other Diseases: Suvorexant, Lemborexant, Daridorexant, and Novel Experimental Agents

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Pitolisant to Treat Excessive Daytime Sleepiness and Cataplexy in Adults with Narcolepsy: Rationale and Clinical Utility

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Narcolepsy and H1N1 influenza immunology a decade later: What have we learned?

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Pitolisant for treating patients with narcolepsy

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Cannabidiol Partially Blocks the Excessive Sleepiness in Hypocretindeficient Rats: Preliminary Data

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Lag Analysis of Fast fMRI Reveals Delayed Information Flow Between the Default Mode and Other Networks in Narcolepsy

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Efficacy of once-nightly sodium oxybate (FT218) in narcolepsy type 1 and type 2: post hoc analysis from the Phase 3 REST-ON Trial

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