Seiji Nishino

Summary

Affiliation: Stanford University
Country: USA

Publications

  1. pmc Histamine from brain resident MAST cells promotes wakefulness and modulates behavioral states
    Sachiko Chikahisa
    Sleep and Circadian Neurobiology Laboratory, Stanford University School of Medicine, Palo Alto, California, United States of America Department of Integrative Physiology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan
    PLoS ONE 8:e78434. 2013
  2. pmc Anti-NMDA-receptor antibody detected in encephalitis, schizophrenia, and narcolepsy with psychotic features
    Ko Tsutsui
    Akita University, Department of Neuropsychiatry, Akita, Japan
    BMC Psychiatry 12:37. 2012
  3. pmc Reduced expression of TAC1, PENK and SOCS2 in Hcrtr-2 mutated narcoleptic dog brain
    Julia Lindberg
    Evolutionary Biology Centre, Department of Evolution, Genomics and Systematics, Uppsala University, Norbyvagen 18D, Uppsala, Sweden
    BMC Neurosci 8:34. 2007
  4. pmc Polymorphisms within the canine MLPH gene are associated with dilute coat color in dogs
    Ute Philipp
    Institute of Animal Breeding and Genetics, University of Veterinary Medicine Hannover, Bunteweg 17p, 30559 Hannover, Germany
    BMC Genet 6:34. 2005
  5. ncbi request reprint Low cerebrospinal fluid hypocretin (Orexin) and altered energy homeostasis in human narcolepsy
    S Nishino
    Stanford University Center for Narcolepsy, Palo Alto, CA 94304, USA
    Ann Neurol 50:381-8. 2001
  6. ncbi request reprint Decreased brain histamine content in hypocretin/orexin receptor-2 mutated narcoleptic dogs
    S Nishino
    Stanford University Center for Narcolepsy, 701B, First Floor, Palo Alto, CA 94304, USA
    Neurosci Lett 313:125-8. 2001
  7. ncbi request reprint Narcolepsy: pathophysiology and pharmacology
    Seiji Nishino
    Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA
    J Clin Psychiatry 68:9-15. 2007
  8. ncbi request reprint The hypocretin/orexin receptor: therapeutic prospective in sleep disorders
    Seiji Nishino
    Center for Narcolepsy Research, 1201 Welch Road, MSLS Building, P 213, Palo Alto, CA 94304 5789, USA
    Expert Opin Investig Drugs 16:1785-97. 2007
  9. ncbi request reprint CSF hypocretin levels in Guillain-Barré syndrome and other inflammatory neuropathies
    S Nishino
    Stanford University Center for Narcolepsy, Palo Alto, CA 94304, USA
    Neurology 61:823-5. 2003
  10. pmc Clinical and neurobiological aspects of narcolepsy
    Seiji Nishino
    Stanford University School of Medicine, Department of Psychiatry and Behavioral Sciences, Sleep and Circadian, Neurobiology Laboratory, Center for Narcolepsy, 1201 Welch Road, P213, Palo Alto, CA 94304, USA
    Sleep Med 8:373-99. 2007

Research Grants

Collaborators

Detail Information

Publications96

  1. pmc Histamine from brain resident MAST cells promotes wakefulness and modulates behavioral states
    Sachiko Chikahisa
    Sleep and Circadian Neurobiology Laboratory, Stanford University School of Medicine, Palo Alto, California, United States of America Department of Integrative Physiology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan
    PLoS ONE 8:e78434. 2013
    ..Our findings suggest that histamine released from brain mast cells is wake-promoting, and emphasizes the physiological and pharmacological importance of brain mast cells in the regulation of sleep and fundamental neurobehavior. ..
  2. pmc Anti-NMDA-receptor antibody detected in encephalitis, schizophrenia, and narcolepsy with psychotic features
    Ko Tsutsui
    Akita University, Department of Neuropsychiatry, Akita, Japan
    BMC Psychiatry 12:37. 2012
    ..These symptoms often occur in young females with ovarian teratomas and are frequently associated with serum and CSF autoantibodies to the NMDA receptor (NMDAR)...
  3. pmc Reduced expression of TAC1, PENK and SOCS2 in Hcrtr-2 mutated narcoleptic dog brain
    Julia Lindberg
    Evolutionary Biology Centre, Department of Evolution, Genomics and Systematics, Uppsala University, Norbyvagen 18D, Uppsala, Sweden
    BMC Neurosci 8:34. 2007
    ..However, little is known about molecular alterations downstream of the hypocretin signals...
  4. pmc Polymorphisms within the canine MLPH gene are associated with dilute coat color in dogs
    Ute Philipp
    Institute of Animal Breeding and Genetics, University of Veterinary Medicine Hannover, Bunteweg 17p, 30559 Hannover, Germany
    BMC Genet 6:34. 2005
    ..In humans and mice a comparable pigmentation phenotype without any documented hair loss is caused by mutations within the melanophilin gene (MLPH)...
  5. ncbi request reprint Low cerebrospinal fluid hypocretin (Orexin) and altered energy homeostasis in human narcolepsy
    S Nishino
    Stanford University Center for Narcolepsy, Palo Alto, CA 94304, USA
    Ann Neurol 50:381-8. 2001
    ..Increased BMI and leptin indicate altered energy homeostasis. Sleep and energy metabolism are likely to be functionally connected through the hypocretin system...
  6. ncbi request reprint Decreased brain histamine content in hypocretin/orexin receptor-2 mutated narcoleptic dogs
    S Nishino
    Stanford University Center for Narcolepsy, 701B, First Floor, Palo Alto, CA 94304, USA
    Neurosci Lett 313:125-8. 2001
    ..Considering the fact that histamine promotes wakefulness, decreases in histaminergic neurotransmission may also account for the sleep abnormalities in hypocretin-deficient narcolepsy...
  7. ncbi request reprint Narcolepsy: pathophysiology and pharmacology
    Seiji Nishino
    Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA
    J Clin Psychiatry 68:9-15. 2007
    ..Hypocretin replacement is also likely to be a new therapeutic option for hypocretin-deficient narcolepsy, but is still not available in humans. In this review, the pharmacologic and pathophysiologic aspects of narcolepsy are discussed...
  8. ncbi request reprint The hypocretin/orexin receptor: therapeutic prospective in sleep disorders
    Seiji Nishino
    Center for Narcolepsy Research, 1201 Welch Road, MSLS Building, P 213, Palo Alto, CA 94304 5789, USA
    Expert Opin Investig Drugs 16:1785-97. 2007
    ....
  9. ncbi request reprint CSF hypocretin levels in Guillain-Barré syndrome and other inflammatory neuropathies
    S Nishino
    Stanford University Center for Narcolepsy, Palo Alto, CA 94304, USA
    Neurology 61:823-5. 2003
    ..Hypocretin-1 levels were moderately reduced in an additional 11 GBS, 5 Miller-Fisher syndrome, and 1 CIDP subject. Low levels in GBS occurred early in the disease and were associated with upper CNS level abnormalities...
  10. pmc Clinical and neurobiological aspects of narcolepsy
    Seiji Nishino
    Stanford University School of Medicine, Department of Psychiatry and Behavioral Sciences, Sleep and Circadian, Neurobiology Laboratory, Center for Narcolepsy, 1201 Welch Road, P213, Palo Alto, CA 94304, USA
    Sleep Med 8:373-99. 2007
    ..In this review, the clinical, pathophysiological and pharmacological aspects of narcolepsy are discussed...
  11. ncbi request reprint The hypothalamic peptidergic system, hypocretin/orexin and vigilance control
    Seiji Nishino
    Center for Narcolepsy, Stanford University, 1201 Welch Road, MSLS, P213 Palo Alto, CA 94304, USA
    Neuropeptides 41:117-33. 2007
    ..Narcolepsy is therefore, an important model to study the link between sleep regulation and other fundamental hypothalamic functions...
  12. ncbi request reprint Symptomatic narcolepsy, cataplexy and hypersomnia, and their implications in the hypothalamic hypocretin/orexin system
    Seiji Nishino
    Center for Narcolepsy, Stanford University, Palo Alto, CA 94304, USA
    Sleep Med Rev 9:269-310. 2005
    ..It appears that further studies of the involvement of the hypocretin system in symptomatic narcolepsy and EDS are helpful to understand the pathophysiological mechanisms for the occurrence of EDS and cataplexy...
  13. ncbi request reprint Neuropeptides as possible targets in sleep disorders
    Seiji Nishino
    Stanford University School of Medicine, Department of Psychiatry and Behavioural Sciences, Sleep and Circadian Neurobiology Laboratory and Center for Narcolepsy Research, Palo Alto, CA 94304 5489, USA
    Expert Opin Ther Targets 11:37-59. 2007
    ..Finally, general strategies for the pharmacological therapeutics targeting the peptidergic systems for sleep disorders are discussed...
  14. doi request reprint Armodafinil for excessive daytime sleepiness
    Seiji Nishino
    Sleep and Circadian Neurobiology Laboratory, Center for Narcolepsy, Stanford University School of Medicine, Palo Alto, CA 94304 5489, USA
    Drugs Today (Barc) 44:395-414. 2008
    ..The commercial challenge to armodafinil may come from generic modafinil, which may become available in 2012, as well as from classical amphetamine and amphetamine-like compounds (for the treatment of narcolepsy)...
  15. doi request reprint Hypothalamus, hypocretins/orexin, and vigilance control
    Seiji Nishino
    Center for Narcolepsy, Stanford University, Palo Alto, CA, USA
    Handb Clin Neurol 99:765-82. 2011
    ..In this chapter, the role of the hypothalamus in vigilance control is discussed, with a particular emphasis on the hypocretins/orexin system...
  16. pmc Decreased CSF histamine in narcolepsy with and without low CSF hypocretin-1 in comparison to healthy controls
    Seiji Nishino
    Sleep and Circadian Neurobiology Laboratory, Center for Narcolepsy, Stanford Sleep Research Center, Stanford University, MSLS Bldg Room P213, 1201 Welch Road, Palo Alto CA 94305, USA
    Sleep 32:175-80. 2009
    ..To examine whether cerebrospinal fluid (CSF) histamine contents are altered in human narcolepsy and whether these alterations are specific to hypocretin deficiency, as defined by low CSF hypocretin-1...
  17. doi request reprint Emerging treatments for narcolepsy and its related disorders
    Seiji Nishino
    Stanford University School of Medicine, USA
    Expert Opin Emerg Drugs 15:139-58. 2010
    ..Over 90% of diagnosed narcoleptic patients are currently prescribed medications to control their symptoms; however, available treatments are merely symptomatic...
  18. pmc Hypocretin/orexin and narcolepsy: new basic and clinical insights
    S Nishino
    Stanford University, Sleep and Circadian Neurobiology Laboratory, Palo Alto, CA 94304 5489, USA
    Acta Physiol (Oxf) 198:209-22. 2010
    ..As a large majority of human narcolepsy patients are ligand deficient, hypocretin replacement therapy may be a promising new therapeutic option, and animal experiments using gene therapy and cell transplantations are in progress...
  19. pmc Effects of paraxanthine and caffeine on sleep, locomotor activity, and body temperature in orexin/ataxin-3 transgenic narcoleptic mice
    Masashi Okuro
    Sleep and Circadian Neurobiology Laboratory, Stanford University, MSLS Bldg Room P213, 1201 Welch Road, Palo Alto, CA 94304, USA
    Sleep 33:930-42. 2010
    ..Caffeine is metabolized to paraxanthine, theobromine, and theophylline. Paraxanthine is a central nervous stimulant and exhibits higher potency at A1 and A2 receptors, but has lower toxicity and lesser anxiogenic effects than caffeine...
  20. pmc Specificity of direct transition from wake to REM sleep in orexin/ataxin-3 transgenic narcoleptic mice
    Nobuhiro Fujiki
    Stanford University Center for Narcolepsy, Palo Alto, CA 94035, USA
    Exp Neurol 217:46-54. 2009
    ..Our definition of DREM in murine narcolepsy may provide good electrophysiological measures for cataplexy-equivalent episodes...
  21. pmc Sleep/wake fragmentation disrupts metabolism in a mouse model of narcolepsy
    Shengwen Zhang
    Psychiatry and Behavioural Sciences, Stanford University, Palo Alto, CA 94304 5742, USA
    J Physiol 581:649-63. 2007
    ..This investigation illustrates the need for coordinated study of multiple phenotypes in mouse models with altered sleep/wake patterns...
  22. ncbi request reprint CSF versus serum leptin in narcolepsy: is there an effect of hypocretin deficiency?
    Isabelle Arnulf
    Center for Narcolepsy, Department of Psychiatry and Behavioral Sciences, Stanford University, Palo Alto, CA, USA
    Sleep 29:1017-24. 2006
    ..To determine if hypocretin deficiency is associated with abnormally low serum leptin levels, a putative cause of increased body mass index in narcoleptics...
  23. pmc Hypocretin receptor expression in canine and murine narcolepsy models and in hypocretin-ligand deficient human narcolepsy
    Kazuo Mishima
    Department of Psychiatry, Stanford University, Center for Narcolepsy, Palo Alto, CA, USA
    Sleep 31:1119-26. 2008
    ..To determine whether hypocretin receptor gene (hcrtR1 and hcrtR2) expression is affected after long-term hypocretin ligand loss in humans and animal models of narcolepsy...
  24. ncbi request reprint Effects of IV and ICV hypocretin-1 (orexin A) in hypocretin receptor-2 gene mutated narcoleptic dogs and IV hypocretin-1 replacement therapy in a hypocretin-ligand-deficient narcoleptic dog
    Nobuhiro Fujiki
    Center for Narcolepsy, Stanford University School of Medicine, Palo Alto, CA 94304 5485, USA
    Sleep 26:953-9. 2003
    ..Using two different canine models of narcolepsy, we evaluated the therapeutic effects of hypocretin-1 on cataplexy and sleep...
  25. ncbi request reprint Conditions of primary excessive daytime sleepiness
    Jed E Black
    Stanford Sleep Disorders Center, Sleep Medicine Division, Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA
    Neurol Clin 23:1025-44. 2005
    ..Several methods have been developed to assess EDS, although each of them has limitations. Treatment is available for the great majority of cases...
  26. doi request reprint Hypocretin ligand deficiency in narcolepsy: recent basic and clinical insights
    Cayde Ritchie
    Center for Narcolepsy, Stanford School of Medicine, Stanford University Sleep and Circadian Neurobiology Laboratory, 1201 Welch Road, MSLS, P213, Palo Alto, CA 94304, USA
    Curr Neurol Neurosci Rep 10:180-9. 2010
    ..Currently, hypocretin replacement therapy has emerged as a promising therapeutic option, and experiments using gene therapy and cell transplantation are in progress...
  27. pmc CSF histamine levels in rats reflect the central histamine neurotransmission
    Atsushi Soya
    Sleep and Circadian Neurobiology Laboratory, Center for Narcolepsy, Psychiatry and Behavioral Sciences, Stanford University, 1201 Welch Road, Palo Alto, CA 94304, USA
    Neurosci Lett 430:224-9. 2008
    ..Our study suggests that CSF histamine levels in rats reflect the central histamine neurotransmission and vigilance state changes, providing deeper insight into the human data...
  28. pmc Time-course of cerebrospinal fluid histamine in the wake-consolidated squirrel monkey
    Jamie M Zeitzer
    Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA
    J Sleep Res 21:189-94. 2012
    ....
  29. ncbi request reprint The role of cerebrospinal fluid hypocretin measurement in the diagnosis of narcolepsy and other hypersomnias
    Emmanuel Mignot
    Center for Narcolepsy, Stanford University, 701B Lower Welch Rd, Palo Alto, CA 94304 5742, USA
    Arch Neurol 59:1553-62. 2002
    ..Narcolepsy, a neurological disorder affecting 1 in 2000 individuals, is associated with HLA-DQB1*0602 and low cerebrospinal fluid (CSF) hypocretin (orexin) levels...
  30. doi request reprint Sleep and EEG features in genetic models of Down syndrome
    Damien Colas
    Center for Narcolepsy, Department of Psychiatry and Behavioral Sciences, Stanford, CA 94305, USA
    Neurobiol Dis 30:1-7. 2008
    ..These results demonstrate abnormalities in sleep and EEG in Ts65Dn mice and underscore a possible correlation between App overexpression and hippocampal theta oscillations...
  31. doi request reprint Refeeding after a 24-hour fasting deepens NREM sleep in a time-dependent manner
    Noriyuki Shimizu
    Department of Integrative Physiology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770 8503, Japan
    Physiol Behav 104:480-7. 2011
    ..Level of NPY mRNA in the arcuate nucleus was increased before the refeeding only at ZT1. These results suggest that refeeding after a 24-h fasting makes NREM sleep deeper in a time-dependent manner...
  32. pmc Predictors of hypocretin (orexin) deficiency in narcolepsy without cataplexy
    Olivier Andlauer
    Center for Sleep Sciences and Medicine, and Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, CA, USA
    Sleep 35:1247-55F. 2012
    ..To compare clinical, electrophysiologic, and biologic data in narcolepsy without cataplexy with low (≤ 110 pg/ml), intermediate (110-200 pg/ml), and normal (> 200 pg/ml) concentrations of cerebrospinal fluid (CSF) hypocretin-1...
  33. ncbi request reprint Sleeping with the hypothalamus: emerging therapeutic targets for sleep disorders
    Emmanuel Mignot
    Stanford University Center for Narcolepsy, 701 Welch Road B, Room 145, Palo Alto, California 94304 5742, USA
    Nat Neurosci 5:1071-5. 2002
    ..Here we highlight the role of the hypothalamus in sleep physiology and discuss neurotransmitter systems, such as adenosine, dopamine, GABA, histamine and hypocretin, that may have therapeutic applications for sleep disorders...
  34. ncbi request reprint A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains
    C Peyron
    Center for Narcolepsy, Stanford University Medical School 1201 Welch Road, Stanford, California 94305 5485, USA
    Nat Med 6:991-7. 2000
    ..Although hypocretin loci do not contribute significantly to genetic predisposition, most cases of human narcolepsy are associated with a deficient hypocretin system...
  35. ncbi request reprint Lesions of the suprachiasmatic nucleus eliminate the daily rhythm of hypocretin-1 release
    Shengwen Zhang
    Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, CA, USA
    Sleep 27:619-27. 2004
    ..The effect of lesions of the suprachiasmatic nucleus (SCN) on hypocretin-1 in the cerebrospinal fluid (CSF) was examined...
  36. ncbi request reprint The hypocretin/orexin system in health and disease
    Seiji Nishino
    Center for Narcolepsy, Stanford University, School of Medicine, Psychiatry and Behavioral Sciences, Palo Alto, California 94304, USA
    Biol Psychiatry 54:87-95. 2003
    ..Hypocretin-deficient human narcolepsy appears to be a more complex condition than a simple sleep disorder, and it may serve as an important disease model for studying hypothalamic function in health and disease...
  37. ncbi request reprint Comparative effects of modafinil and amphetamine on daytime sleepiness and cataplexy of narcoleptic dogs
    J Shelton
    Sleep Research Center, Stanford University School of Medicine, Palo Alto, California 94304, USA
    Sleep 18:817-26. 1995
    ..This finding is consistent with the data collected in human narcolepsy and validates the use of this canine model for the screening of stimulant compounds...
  38. ncbi request reprint Fluctuation of extracellular hypocretin-1 (orexin A) levels in the rat in relation to the light-dark cycle and sleep-wake activities
    Y Yoshida
    Stanford University Center for Narcolepsy, 701B Welch Rd, 1st Floor, Palo Alto, CA 94304, USA
    Eur J Neurosci 14:1075-81. 2001
    ....
  39. doi request reprint The neurochemistry of awakening: findings from sleep disorder narcolepsy
    Seiji Nishino
    Sleep and Circadian Neurobiology Laboratory, Stanford University School of Medicine, Stanford, CA 94304 5489, USA
    Int Rev Neurobiol 93:229-55. 2010
    ..Similarly, the pathophysiology of idiopathic hypersomnia, another defined primary hypersomnia, is largely unknown. This chapter discusses our current understanding of the neurochemistry of EDS, a disease of awakening...
  40. pmc Sex difference in body weight gain and leptin signaling in hypocretin/orexin deficient mouse models
    Nobuhiro Fujiki
    Center for Narcolepsy, Stanford Sleep Research Center, 701B Welch Rd, Palo Alto, CA 94304, United States
    Peptides 27:2326-31. 2006
    ..However, multiple factors are also likely to affect this phenotype, and a sex difference specific alteration of leptin-hypocretin signaling may be involved...
  41. ncbi request reprint The roles of midbrain and diencephalic dopamine cell groups in the regulation of cataplexy in narcoleptic Dobermans
    Mutsumi Okura
    Center for Narcolepsy, Stanford Sleep Center, Stanford University School of Medicine, Palo Alto, CA 94304 5485, USA
    Neurobiol Dis 16:274-82. 2004
    ..e., autoreceptors) for the regulation of cataplexy. Because the A11 cell group projects to the spinal ventral horn, the A11 D(2/3) receptive mechanisms may directly modulate the activity of spinal motoneurons and modulate cataplexy...
  42. pmc Using iPSC-derived neurons to uncover cellular phenotypes associated with Timothy syndrome
    Sergiu P Paşca
    Department of Neurobiology, Stanford University School of Medicine, Stanford, California, USA
    Nat Med 17:1657-62. 2011
    ..These findings provide strong evidence that Ca(v)1.2 regulates the differentiation of cortical neurons in humans and offer new insights into the causes of autism in individuals with Timothy syndrome...
  43. ncbi request reprint CSF hypocretin-1 levels in schizophrenics and controls: relationship to sleep architecture
    Seiji Nishino
    Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, CA 94305, USA
    Psychiatry Res 110:1-7. 2002
    ..Further studies of whether CNS hypocretin neurotransmission is involved in sleep and neuroendocrine abnormalities seen in patients with schizophrenia and other psychiatric conditions are warranted...
  44. ncbi request reprint The neurobiology of hypocretins (orexins), narcolepsy and related therapeutic interventions
    Jamie M Zeitzer
    Department of Psychiatry, Stanford University, 701 B Welch Road, Palo Alto, CA 94304, USA
    Trends Pharmacol Sci 27:368-74. 2006
    ..Hypocretin receptor agonists are likely to be ideal therapeutic options for hypocretin-deficient narcolepsy but such compounds are still not available in humans...
  45. ncbi request reprint Differential kinetics of hypocretins in the cerebrospinal fluid after intracerebroventricular administration in rats
    Yasushi Yoshida
    Center for Narcolepsy, Stanford University, 701B Welch Road, 1st Floor, Palo Alto, CA, 94304 5742, USA
    Neurosci Lett 346:182-6. 2003
    ..Difference in the kinetics of hypocretins should be considered for interpreting ICV effects of hypocretins...
  46. ncbi request reprint Narcoleptic canines display periodic leg movements during sleep
    M Okura
    Center for Narcolepsy, Sleep Research Center, Department of Psychiatry and Behavioral Sciences, Stanford University, Palo Alto, California, USA
    Psychiatry Clin Neurosci 55:243-4. 2001
    ..Our canines may therefore be an invaluable resource in PLMS research...
  47. ncbi request reprint Hypocretin levels in sporadic and familial cases of canine narcolepsy
    B Ripley
    Center for Narcolepsy, Stanford Sleep Center, Stanford University School of Medicine, Palo Alto, California 94304, USA
    Neurobiol Dis 8:525-34. 2001
    ..The presence of hypocretin peptides in Hcrtr 2-mutated animals suggests that neurotransmission through Hcrtr 1 may be intact, arguing for a preferential importance of Hcrtr 2-mediated function in narcolepsy...
  48. pmc Tuning arousal with optogenetic modulation of locus coeruleus neurons
    MATTHEW E CARTER
    Neurosciences Program, Stanford University, Stanford, California, USA
    Nat Neurosci 13:1526-33. 2010
    ..These results suggest that the locus coeruleus is finely tuned to regulate organismal arousal and that bursts of noradrenergic overexcitation cause behavioral attacks that resemble those seen in people with neuropsychiatric disorders...
  49. ncbi request reprint Neuropeptides as possible targets in sleep disorders: special emphasis on hypocretin-deficient narcolepsy
    Nobuhiro Fujiki
    Sleep and Circadian Neurobiology Laboratory, Center for Narcolepsy, Stanford University School of Medicine, 1201 Welch Road, Lucas MSLS Building, P213, Palo Alto, CA 94304 5789, USA
    CNS Neurol Disord Drug Targets 6:45-62. 2007
    ....
  50. ncbi request reprint Emerging therapies in narcolepsy-cataplexy
    Emmanuel Mignot
    Howard Hughes Medical Research Institute, Stanford University School of Medicine, Stanford, CA, USA
    Sleep 28:754-63. 2005
    ..We also report on novel strategies designed to compensate for hypocretin deficiency and on the use of immunosupression at the time of narcolepsy onset...
  51. ncbi request reprint An activation of parvocellular oxytocinergic neurons in the paraventricular nucleus in oxytocin-induced yawning and penile erection
    Ichiro Kita
    Sleep and Circadian Neurobiology Laboratory, Center for Narcolepsy, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, CA 94304 5489, USA
    Neurosci Res 54:269-75. 2006
    ....
  52. ncbi request reprint Analysis of onset location, laterality and propagation of cataplexy in canine narcolepsy
    Nobuhiro Fujiki
    Center for Narcolepsy, Stanford University School of Medicine, Palo Alto 94304, United States of America
    Psychiatry Clin Neurosci 56:275-6. 2002
    ..Involvement of abnormal inactivation of bilateral pathways to the spinal motoneurones due to a deficiency in hypocretin neurotransmission is suggested in the occurrence of cataplexy...
  53. ncbi request reprint Cholinergic regulation of cataplexy in canine narcolepsy in the pontine reticular formation is mediated by M2 muscarinic receptors
    M S Reid
    Stanford University, Sleep Disorders Research Center, Palo Alto, California 94304
    Sleep 17:424-35. 1994
    ..The effects of muscimol indicate that the stimulation of cataplexy might be elicited by local neuronal inhibition...
  54. ncbi request reprint Circadian distribution of rest/activity in narcoleptic and control dogs: assessment with ambulatory activity monitoring
    S Nishino
    Sleep Disorders Center, Stanford University School of Medicine, CA, USA
    J Sleep Res 6:120-7. 1997
    ..Ambulatory activity monitoring may be a useful non-invasive method for future pharmacological and development studies in the narcoleptic canine model...
  55. ncbi request reprint Neuropharmacology and neurochemistry of canine narcolepsy
    S Nishino
    Sleep Research Center, Stanford University School of Medicine, Palo Alto, California
    Sleep 17:S84-92. 1994
    ....
  56. ncbi request reprint Increased dopaminergic transmission mediates the wake-promoting effects of CNS stimulants
    S Nishino
    Stanford University School of Medicine, Sleep Disorders Center, Palo Alto, CA 94304, USA
    Sleep Res Online 1:49-61. 1998
    ..Our results also suggest that presynaptic activation of DA transmission is a key pharmacological property mediating the wake-promoting effects of currently available CNS stimulants...
  57. ncbi request reprint Dopaminergic role in stimulant-induced wakefulness
    J P Wisor
    Sleep Disorders Research Center, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California 94305, USA
    J Neurosci 21:1787-94. 2001
    ..Thus, dopamine transporters play an important role in sleep regulation and are necessary for the specific wake-promoting action of amphetamines and modafinil...
  58. ncbi request reprint Is narcolepsy a REM sleep disorder? Analysis of sleep abnormalities in narcoleptic Dobermans
    S Nishino
    Center for Narcolepsy, Stanford Sleep Center, Stanford University School of Medicine, 1201 Welch Road, MSLS Building Room P113, Palo Alto, CA 94304 5485, USA
    Neurosci Res 38:437-46. 2000
    ..Cataplexy and a dysfunction in the maintenance of vigilance states, but not abnormal REM sleep generation, may therefore be central to narcolepsy...
  59. ncbi request reprint Changes in CSF hypocretin-1 (orexin A) levels in rats across 24 hours and in response to food deprivation
    N Fujiki
    Stanford University Center for Narcolepsy, Palo Alto, CA 94304 USA
    Neuroreport 12:993-7. 2001
    ..These results indicate an important link between circadian control of sleep and energy homeostasis via the hypocretin system...
  60. ncbi request reprint Drug treatment of patients with insomnia and excessive daytime sleepiness: pharmacokinetic considerations
    S Nishino
    Stanford Center for Narcolepsy, Stanford University, School of Medicine, Palo Alto, California 94304, USA
    Clin Pharmacokinet 37:305-30. 1999
    ..In this review, we will introduce recently obtained knowledge of the pharmacokinetics of hypnosedatives and CNS stimulants and their applications for patients affected with insomnia and EDS...
  61. ncbi request reprint Cerebrospinal fluid prostaglandins and corticotropin releasing factor in schizophrenics and controls: relationship to sleep architecture
    S Nishino
    Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, CA 94305, USA
    Psychiatry Res 78:141-50. 1998
    ..These results do not favor the hypothesis of a role for CRF or PGs in the pathophysiology of sleep disturbances in schizophrenia...
  62. ncbi request reprint The sleep disorder canine narcolepsy is caused by a mutation in the hypocretin (orexin) receptor 2 gene
    L Lin
    Center for Narcolepsy, Department of Psychiatry, Stanford University School of Medicine, California 94305 5485, USA
    Cell 98:365-76. 1999
    ..This result identifies hypocretins as major sleep-modulating neurotransmitters and opens novel potential therapeutic approaches for narcoleptic patients...
  63. ncbi request reprint Addiction and arousal: alternative roles of hypothalamic peptides
    Luis de Lecea
    Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California 94305, USA
    J Neurosci 26:10372-5. 2006
    ..This review summarizes a Mini-Symposium presented at the 2006 Annual Meeting of the Society for Neuroscience...
  64. ncbi request reprint CSF hypocretin/orexin levels in narcolepsy and other neurological conditions
    B Ripley
    Stanford University Center for Narcolepsy, Palo Alto, CA 94304, USA
    Neurology 57:2253-8. 2001
    ..Future research in this area is needed to establish functional significance...
  65. ncbi request reprint Measurement of hypocretin/orexin content in the mouse brain using an enzyme immunoassay: the effect of circadian time, age and genetic background
    L Lin
    Department of Psychiatry and Behavior Sciences, Center for Narcolepsy and Sleep Disorder, Stanford University, Palo Alto, CA 94304 5742, USA
    Peptides 23:2203-11. 2002
    ..Compared to controls, only histamine receptor knockouts had lower hypocretin levels. This was most pronounced in H1 receptor knockouts suggesting the existence of a positive feedback loop between hypocretin and histaminergic neurons...
  66. ncbi request reprint Desmethyl metabolites of serotonergic uptake inhibitors are more potent for suppressing canine cataplexy than their parent compounds
    S Nishino
    Sleep Research Center, Stanford University School of Medicine, Palo Alto, California 94304
    Sleep 16:706-12. 1993
    ..Our results also suggest that the anticataplectic effect of "selective" serotonergic uptake inhibitors in human narcolepsy might be mediated by their less selective active metabolites...
  67. ncbi request reprint Mesopontine organization of cholinergic and catecholaminergic cell groups in the normal and narcoleptic dog
    M Tafti
    Center for Narcolepsy Research, Stanford University, Palo Alto, California 94304, USA
    J Comp Neurol 379:185-97. 1997
    ..In conclusion, the present results do not support the hypothesis that the neurochemical imbalance in narcolepsy could result from abnormal organization, numbers, or ratio of the corresponding neuronal populations...
  68. ncbi request reprint Hypocretin stimulates [(35)S]GTP gamma S binding in Hcrtr 2-transfected cell lines and in brain homogenate
    T Shiba
    Center for Narcolepsy, Stanford University, 701B Welch Rd, Palo Alto, CA 94304, USA
    Biochem Biophys Res Commun 294:615-20. 2002
    ..Hypocretin-stimulated [(35)S]GTP gamma S binding, may thus be a useful functional assay for hypocretin receptors in both cell lines and brain tissue homogenates...
  69. ncbi request reprint [The US Government's effort in decreasing the cost of sleep-related problems and its outcome]
    You Hwi Song
    Department of Psychiatry, Sleep Circadian and Neurobiology Laboratory, Center for Narcolepsy Research, School of Medicine, Stanford University, Palo Alto, California 94305, USA
    J UOEH 30:329-52. 2008
    ....
  70. ncbi request reprint Narcolepsy and syndromes of primary excessive daytime somnolence
    Jed E Black
    Stanford Sleep Disorders Center, Stanford University, California, USA
    Semin Neurol 24:271-82. 2004
    ..Finally, in view of the tremendous advances that have occurred in the past few years in our understanding of the pathophysiology of canine and human narcolepsy, we also highlight these discoveries...
  71. ncbi request reprint Narcolepsy and cataplexy
    Seiji Nishino
    Stanford University School of Medicine and Center for Narcolepsy, Stanford Sleep Research Center, Palo Alto, CA, USA Circadian Neurobiology Laboratory, Palo Alto, CA, USA
    Handb Clin Neurol 99:783-814. 2011
    ..This chapter starts with an overview of the clinical aspects of narcolepsy, followed by an update on the pathophysiology. Finally, we discuss the expectations from future narcolepsy research...
  72. pmc The diurnal rhythm of hypocretin in young and old F344 rats
    Frank Desarnaud
    West Roxbury Veterans Affairs Medical Center and Harvard Medical School, Mass 02132, USA
    Sleep 27:851-6. 2004
    ..In young rats and monkeys, levels of HCRT-1 are highest at the end of the wake-active period and lowest toward the end of the sleep period. However, the effects of age on the diurnal rhythm of HCRT-1 are not known...
  73. ncbi request reprint CSF hypocretin-1 (orexin-A) concentrations in narcolepsy with and without cataplexy and idiopathic hypersomnia
    Takashi Kanbayashi
    Department of Neuropsychiatry, Akita University School of Medicine, Hondo, Akita
    J Sleep Res 11:91-3. 2002
    ..Low CSF hypocretin-1 is therefore very specific for HLA DR2 positive narcolepsy-cataplexy, and the deficiency is likely to be established at the early stage of the disease...
  74. ncbi request reprint Acute effects of zolpidem on daytime alertness, psychomotor and physical performance
    Sachiko Uemura Ito
    Akita University, School of Health Sciences, Course of Physical Therapy 1 1 1 Hondo, Akita, Akita 0108543, Japan
    Neurosci Res 59:309-13. 2007
    ....
  75. ncbi request reprint Hypocretin-1 (orexin-A) levels in human lumbar CSF in different age groups: infants to elderly persons
    Takashi Kanbayashi
    Department of Neuropsychiatry, Akita University School of Medicine, Hondo, Japan
    Sleep 25:337-9. 2002
    ..In this study, we measured CSF hypocretin-1 levels in various age ranges from infants to elder people to investigate the age-dependent change of hypocretin concentrations...
  76. ncbi request reprint CSF orexin-A/hypocretin-1 concentrations in patients with intracerebral hemorrhage (ICH)
    Kenji Dohi
    Showa University, Department of Emergency and Critical Care Medicine, School of Medicine, 1 5 8 Hatanodai, Shinagawa ku, Tokyo, Japan
    Regul Pept 145:60-4. 2008
    ..3 pg/ml vs. 65.2+/-21.2 pg/ml; p=0.03.) These data indicate that orexin-A/hypocretin-1 may therefore play an important role in the various physiological responses including sleep, feeding, and the overall metabolism in ICH patients...
  77. ncbi request reprint Hypersomnolence and increased REM sleep with low cerebrospinal fluid hypocretin level in a patient after removal of craniopharyngioma
    Naoko Tachibana
    Osaka Medical Center for Health Sciences and Promotion, Japan
    Sleep Med 6:567-9. 2005
    ..A more global hypothalamic lesion demonstrated by brain magnetic resonance imaging (MRI) after surgery seemed to cause marked disinhibition of REM sleep as well as hypersomnolence in this patient...
  78. ncbi request reprint Diurnal variation of cerebrospinal fluid hypocretin-1 (Orexin-A) levels in control and depressed subjects
    Ronald M Salomon
    Department of Psychiatry, Vanderbilt University School of Medicine, Nashville, Tennessee 37212, USA
    Biol Psychiatry 54:96-104. 2003
    ..Shortened rapid eye movement latency is observed in both narcolepsy and depression. Cerebrospinal fluid hypocretin-1 levels have not been reported in mood disorders...
  79. ncbi request reprint Enhanced antinociception by intracerebroventricularly and intrathecally-administered orexin A and B (hypocretin-1 and -2) in mice
    Jalal Izadi Mobarakeh
    Department of Pharmacology, Tohoku University School of Medicine, Seiryo machi 2 1, Aoba ku, Sendai 980 8575, Japan
    Peptides 26:767-77. 2005
    ..The present findings suggest that orexins have an antinociceptive role in at least four different types of pains, probably acting on both the brain and spinal cord...
  80. ncbi request reprint The narcoleptic borderland: a multimodal diagnostic approach including cerebrospinal fluid levels of hypocretin-1 (orexin A)
    Claudio Bassetti
    Department of Neurology, University Hospital, Bern, Switzerland
    Sleep Med 4:7-12. 2003
    ..The clinical borderland of narcolepsy and the diagnostic value of different markers of narcolepsy remain controversial and were assessed in a consecutive series of 27 patients with hypersomnia of (mainly) neurological origin...
  81. ncbi request reprint Increased hypocretin-1 levels in cerebrospinal fluid after REM sleep deprivation
    Mario Pedrazzoli
    Department of Psychobiology Sleep Institute, Universidade Federal de Sao Paulo, Rua Napoleao de Barros 925, Sao Paulo, SP, CEP 04024 002, Brazil
    Brain Res 995:1-6. 2004
    ..Increased hypocretin tone during REM deprivation may be important in mediating some of the effects of REM sleep deprivation such as antidepressant effects, hyperphagia and increased sympathetic activity...
  82. ncbi request reprint Mistaken diagnosis of psychogenic gait disorder in a man with status cataplecticus ("limp man syndrome")
    David K Simon
    Beth Israel Deaconess Medical Center and Harvard Medical School, Department of Neurology, Boston, Massachusetts 02115, USA
    Mov Disord 19:838-40. 2004
    ..The gait difficulties resolved with venlafaxine. This case demonstrates that status cataplecticus can be misdiagnosed as a psychogenic gait disorder...
  83. ncbi request reprint Relationship between CSF hypocretin levels and hypocretin neuronal loss
    Dmitry Gerashchenko
    West Roxbury VA Medical Center and Harvard Medical School, West Roxbury, MA 02132, USA
    Exp Neurol 184:1010-6. 2003
    ..In those narcoleptics where CSF levels are within the normal range, it is possible that not all of the HCRT neurons are lost and that the surviving HCRT neurons might be increasing output of CSF HCRT...
  84. ncbi request reprint Narcolepsy caused by acute disseminated encephalomyelitis
    Richard F Gledhill
    Department of Neurology, Medical University of Southern Africa, Ga Rankuwa Hospital, Pretoria, Republic of South Africa
    Arch Neurol 61:758-60. 2004
    ..Narcolepsy with cataplexy is caused by a selective loss of hypocretin-producing neurons, but narcolepsy can also result from hypothalamic and rostral brainstem lesions...
  85. ncbi request reprint Enhanced antinociception by intracerebroventricularly administered orexin A in histamine H1 or H2 receptor gene knockout mice
    Jalal Izadi Mobarakeh
    Department of Pharmacology, Tohoku University School of Medicine, Seiryo machi 2 1, Sendai 980 8575, Japan
    Pain 118:254-62. 2005
    ..Thus, the blocking of the histamine H1 or H2 receptor may produce antinociception and enhance the orexin A-induced antinociception...
  86. ncbi request reprint Sleep disturbances and hypocretin deficiency in Niemann-Pick disease type C
    Jitka Vankova
    Department of Neurology, 1st Medical Faculty, Charles University, Prague
    Sleep 26:427-30. 2003
    ..HLA typing and cerebrospinal fluid hypocretin levels were also evaluated in 4 patients. Niemann-Pick disease diagnosis was confirmed in all cases biochemically and by the presence of foam cells in the bone marrow...
  87. ncbi request reprint [An old and new focal symptom, hypothalamus and hypersomnia, orexin system and narcolepsy]
    Takashi Kanbayashi
    Rinsho Shinkeigaku 45:824-7. 2005
  88. ncbi request reprint Hypocretin-1 (orexin-A) concentrations in cerebrospinal fluid are low in patients with Guillain-Barré syndrome
    Takashi Kanbayashi
    Department of Neuropsychiatry, Akita University School of Medicine, Japan
    Psychiatry Clin Neurosci 56:273-4. 2002
    ..The results of the present study indicate that some patients with GBS have lower levels of CSF hypocretin-1...
  89. ncbi request reprint HLA and hypocretin studies in Korean patients with narcolepsy
    Seung Chul Hong
    Department of Neuropsychiatry, St Vincent s Hospital, Catholic University of Korea, Suwon
    Sleep 25:440-4. 2002
    ..Very few studies have evaluated narcolepsy in Asian countries, outside of Japan. Our goal was to study narcolepsy at the genetic, clinical and pathophysiological level in Korea...
  90. ncbi request reprint Transient total sleep loss in cerebral Whipple's disease: a longitudinal study
    Ulrich Voderholzer
    Department of Psychiatry and Psychotherapy, University of Freiburg, Freiburg, Germany
    J Sleep Res 11:321-9. 2002
    ..The extent of sleep disruption in this case of organic insomnia was similar to cases of familial fatal insomnia, but was at least partially reversible with treatment...
  91. ncbi request reprint Inhibition of rostral basal forebrain neurons promotes wakefulness and induces FOS in orexin neurons
    Shinsuke Satoh
    Second Department of Anatomy and Neurobiology, Kinki University School of Medicine, Osaka Sayama, Osaka 589 8511, Japan
    Eur J Neurosci 17:1635-45. 2003
    ..These functional data suggested that a sleep-generating element in the ventromedial part of the rostral basal forebrain provides an inhibitory influence on the activities of the orexin neurons in the tuberal part of the hypothalamus...
  92. ncbi request reprint CSF orexin A concentrations and expressions of the orexin-1 receptor in rat hippocampus after cardiac arrest
    Kenji Dohi
    Department of Emergency and Critical Care Medicine, School of Medicine, Showa University, Shinagawa ku, Tokyo, Japan
    Neuropeptides 40:245-50. 2006
    ..These results suggest that dynamics of orexin signaling observed may have functional roles for neuronal damage associated with transient ischemia...
  93. ncbi request reprint Hypersomnia and low cerebrospinal fluid hypocretin levels in acute disseminated encephalomyelitis
    Sosuke Yoshikawa
    Department of Pediatrics, Osaka Medical College, Osaka, Japan
    Pediatr Neurol 31:367-70. 2004
    ..Decreased hypothalamic hypocretin neurotransmission may be involved in this symptomatic case of hypersomnia associated with acute disseminated encephalomyelitis...
  94. ncbi request reprint Expression pattern of FOS in orexin neurons during sleep induced by an adenosine A2A receptor agonist
    Shinsuke Satoh
    Department of Neuropsychiatry, Osaka Medical College, Takatsuki, Osaka 569 8686, Japan
    Behav Brain Res 170:277-86. 2006
    ..MCH neurons are not likely to change their activities during this sleep-promoting process...
  95. ncbi request reprint Diurnal variation in CSF orexin-A in healthy male subjects
    Scott P Grady
    Portland Diabetes and Endocrinology Center, Portland, OR, USA
    Sleep 29:295-7. 2006
    ..Orexin-A is hypothesized to promote wakefulness, and we examined whether cerebrospinal fluid (CSF) orexin-A levels are higher during the waking period in man...
  96. ncbi request reprint FOS expression in orexin neurons following muscimol perfusion of preoptic area
    Shinsuke Satoh
    Department of Neuropsychiatry, Osaka Medical College, Takatsuki, Osaka 569 8686, Japan
    Neuroreport 15:1127-31. 2004
    ..018 by Wilcoxon signed-rank test). These results suggest that subpopulations of the preoptic neurons give an inhibitory tone to the activities of the orexin neurons in the perifornical/lateral hypothalamic areas...

Research Grants8

  1. PHARMACOLOGICAL STUDIES OF HUMAN AND CANINE NARCOLEPSY
    Seiji Nishino; Fiscal Year: 2002
    ....
  2. Role of Histamine in Narcolepsy/EDS Disorders
    Seiji Nishino; Fiscal Year: 2007
    ..As almost nothing is known on the pathophysiology of non- hypocretin deficient hypersomnias, we believe this work to be ideally suited for a small grant application. ..
  3. Role of hypocretin/histamine in Narcolepsy/EDS disorders
    Seiji Nishino; Fiscal Year: 2007
    ..We believe that results from these studies will bring new insights regarding the roles of the hypocretin/histamine interaction in narcolepsy and other EDS disorders and better treatment modalities in humans. ..
  4. Role of hypocretin/histamine in Narcolepsy/EDS disorders
    Seiji Nishino; Fiscal Year: 2009
    ..We believe that results from these studies will bring new insights regarding the roles of the hypocretin/histamine interaction in narcolepsy and other EDS disorders and better treatment modalities in humans. ..