Hcrt

Summary

Gene Symbol: Hcrt
Description: hypocretin
Alias: PPOX, orexin, orexin A, orexin B, prepro-orexin
Species: mouse
Products:     Hcrt

Top Publications

  1. Hara J, Beuckmann C, Nambu T, Willie J, Chemelli R, Sinton C, et al. Genetic ablation of orexin neurons in mice results in narcolepsy, hypophagia, and obesity. Neuron. 2001;30:345-54 pubmed
    ..Recent reports suggest that loss of orexin-containing neurons occurs in human patients with narcolepsy...
  2. Chemelli R, Willie J, Sinton C, Elmquist J, Scammell T, Lee C, et al. Narcolepsy in orexin knockout mice: molecular genetics of sleep regulation. Cell. 1999;98:437-51 pubmed
    Neurons containing the neuropeptide orexin (hypocretin) are located exclusively in the lateral hypothalamus and send axons to numerous regions throughout the central nervous system, including the major nuclei implicated in sleep ..
  3. Hunsley M, Curtis W, Palmiter R. Behavioral and sleep/wake characteristics of mice lacking norepinephrine and hypocretin. Genes Brain Behav. 2006;5:451-7 pubmed
    We investigated the interaction between norepinephrine (NE) and orexin/hypocretin (Hcrt) in the control of sleep behavior and narcoleptic symptoms by creating mice that were deficient in both neurotransmitters...
  4. Belle M, Hughes A, Bechtold D, Cunningham P, Pierucci M, Burdakov D, et al. Acute suppressive and long-term phase modulation actions of orexin on the mammalian circadian clock. J Neurosci. 2014;34:3607-21 pubmed publisher
    ..For example, neurons containing the neuropeptide orexin homeostatically control arousal and appetitive states, while neurons in the suprachiasmatic nuclei (SCN) function ..
  5. Thankachan S, Kaur S, Shiromani P. Activity of pontine neurons during sleep and cataplexy in hypocretin knock-out mice. J Neurosci. 2009;29:1580-5 pubmed publisher
    Narcolepsy is a human sleep disorder resulting from the loss of neurons containing the neuropeptide orexin, also known as hypocretin...
  6. Tsunematsu T, Kilduff T, Boyden E, Takahashi S, Tominaga M, Yamanaka A. Acute optogenetic silencing of orexin/hypocretin neurons induces slow-wave sleep in mice. J Neurosci. 2011;31:10529-39 pubmed publisher
    b>Orexin/hypocretin neurons have a crucial role in the regulation of sleep and wakefulness...
  7. Akiyama M, Yuasa T, Hayasaka N, Horikawa K, Sakurai T, Shibata S. Reduced food anticipatory activity in genetically orexin (hypocretin) neuron-ablated mice. Eur J Neurosci. 2004;20:3054-62 pubmed
    ..Under these experimental conditions, prepro-orexin mRNA and orexin A immunoreactivity in the lateral hypothalamic area (LHA) did not show daily variation...
  8. Schöne C, Cao Z, Apergis Schoute J, Adamantidis A, Sakurai T, Burdakov D. Optogenetic probing of fast glutamatergic transmission from hypocretin/orexin to histamine neurons in situ. J Neurosci. 2012;32:12437-43 pubmed publisher
    Hypothalamic hypocretin/orexin (hcrt/orx) neurons coordinate sleep-wake cycles, reward seeking, and body energy balance...
  9. Yamanaka A, Muraki Y, Tsujino N, Goto K, Sakurai T. Regulation of orexin neurons by the monoaminergic and cholinergic systems. Biochem Biophys Res Commun. 2003;303:120-9 pubmed
    ..Here we characterize the electrophysiological properties of orexin neurons using slice preparations from transgenic mice in which orexin neurons specifically express green ..

More Information

Publications90

  1. Sakurai T, Amemiya A, Ishii M, Matsuzaki I, Chemelli R, Tanaka H, et al. Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell. 1998;92:573-85 pubmed
    ..These peptides, termed orexin-A and -B, have no significant structural similarities to known families of regulatory peptides...
  2. Liu M, Thankachan S, Kaur S, Begum S, Blanco Centurion C, Sakurai T, et al. Orexin (hypocretin) gene transfer diminishes narcoleptic sleep behavior in mice. Eur J Neurosci. 2008;28:1382-93 pubmed publisher
    ..Narcolepsy is a neurodegenerative sleep disorder linked to the loss of neurons containing the neuropeptide orexin, also known as hypocretin...
  3. CARTER M, Brill J, Bonnavion P, Huguenard J, Huerta R, de Lecea L. Mechanism for Hypocretin-mediated sleep-to-wake transitions. Proc Natl Acad Sci U S A. 2012;109:E2635-44 pubmed
    Current models of sleep/wake regulation posit that Hypocretin (Hcrt)-expressing neurons in the lateral hypothalamus promote and stabilize wakefulness by projecting to subcortical arousal centers...
  4. Sakurai T, Nagata R, Yamanaka A, Kawamura H, Tsujino N, Muraki Y, et al. Input of orexin/hypocretin neurons revealed by a genetically encoded tracer in mice. Neuron. 2005;46:297-308 pubmed
    The finding of orexin/hypocretin deficiency in narcolepsy patients suggests that this hypothalamic neuropeptide plays a crucial role in regulating sleep/wakefulness states...
  5. de Lecea L, Kilduff T, Peyron C, Gao X, Foye P, Danielson P, et al. The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity. Proc Natl Acad Sci U S A. 1998;95:322-7 pubmed
    ..The hypocretin (Hcrt) protein products are restricted to neuronal cell bodies of the dorsal and lateral hypothalamic areas...
  6. CARTER M, Adamantidis A, Ohtsu H, Deisseroth K, de Lecea L. Sleep homeostasis modulates hypocretin-mediated sleep-to-wake transitions. J Neurosci. 2009;29:10939-49 pubmed publisher
    ..Previously, our laboratory demonstrated that in vivo photostimulation of Hcrt neurons genetically targeted with ChR2, a light-activated cation channel, was sufficient to increase the ..
  7. Adamantidis A, Zhang F, Aravanis A, Deisseroth K, de Lecea L. Neural substrates of awakening probed with optogenetic control of hypocretin neurons. Nature. 2007;450:420-4 pubmed
    ..Hypocretin (Hcrt, also known as orexin)-producing neurons in the lateral hypothalamus are important for arousal stability, and loss of Hcrt function has ..
  8. Willie J, Chemelli R, Sinton C, Tokita S, Williams S, Kisanuki Y, 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;38:715-30 pubmed
    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) ..
  9. Kayaba Y, Nakamura A, Kasuya Y, Ohuchi T, Yanagisawa M, Komuro I, et al. Attenuated defense response and low basal blood pressure in orexin knockout mice. Am J Physiol Regul Integr Comp Physiol. 2003;285:R581-93 pubmed
    ..We examined whether orexin, a recently identified hypothalamic neuropeptide, contributes to the defense response and basal cardiovascular ..
  10. Lutter M, Krishnan V, Russo S, Jung S, McClung C, Nestler E. Orexin signaling mediates the antidepressant-like effect of calorie restriction. J Neurosci. 2008;28:3071-5 pubmed publisher
    ..response in two rodent models of depression and that this response is dependent on the hypothalamic neuropeptide orexin (hypocretin)...
  11. Kaur S, Thankachan S, Begum S, Blanco Centurion C, Sakurai T, Yanagisawa M, et al. Entrainment of temperature and activity rhythms to restricted feeding in orexin knock out mice. Brain Res. 2008;1205:47-54 pubmed publisher
    ..In the present study, we investigate whether the neuropeptide orexin, which has been linked to arousal, might transduce the arousal signal...
  12. Clark E, Baumann C, Cano G, Scammell T, Mochizuki T. Feeding-elicited cataplexy in orexin knockout mice. Neuroscience. 2009;161:970-7 pubmed publisher
    Mice lacking orexin/hypocretin signaling have sudden episodes of atonia and paralysis during active wakefulness...
  13. Willie J, Lim M, Bennett R, Azarion A, Schwetye K, Brody D. Controlled cortical impact traumatic brain injury acutely disrupts wakefulness and extracellular orexin dynamics as determined by intracerebral microdialysis in mice. J Neurotrauma. 2012;29:1908-21 pubmed publisher
    Among other deficits, traumatic brain injury (TBI) causes impaired arousal and cognitive dysfunction. Hypothalamic orexin neuropeptides (also called hypocretins) regulate levels of arousal, and cerebrospinal fluid orexin levels are ..
  14. Gunapala K, Gallardo C, Hsu C, Steele A. Single gene deletions of orexin, leptin, neuropeptide Y, and ghrelin do not appreciably alter food anticipatory activity in mice. PLoS ONE. 2011;6:e18377 pubmed publisher
    ..Using the CR model, we then attempted to verify the published result that orexin deletion diminishes food anticipatory activity (FAA) but observed little to no diminution in the response to CR ..
  15. Yoshida T, Semprun Prieto L, Wainford R, Sukhanov S, Kapusta D, Delafontaine P. Angiotensin II reduces food intake by altering orexigenic neuropeptide expression in the mouse hypothalamus. Endocrinology. 2012;153:1411-20 pubmed publisher
    ..Ang II (1 ?g/kg · min) infusion in FVB mice rapidly reduced hypothalamic expression of neuropeptide Y (Npy) and orexin and decreased food intake at 6 h compared with sham-infused controls but did not change peripheral leptin, ghrelin,..
  16. Bonnavion P, Jackson A, CARTER M, de Lecea L. Antagonistic interplay between hypocretin and leptin in the lateral hypothalamus regulates stress responses. Nat Commun. 2015;6:6266 pubmed publisher
    ..Here using optogenetic approaches in mice, we show that neurons that produce hypocretin (Hcrt)/orexin in the lateral hypothalamic area (LHA) regulate corticosterone release and a variety of behaviours and ..
  17. Roh J, Jiang H, Finn M, Stewart F, Mahan T, Cirrito J, et al. Potential role of orexin and sleep modulation in the pathogenesis of Alzheimer's disease. J Exp Med. 2014;211:2487-96 pubmed publisher
    ..Orexins (hypocretins) initiate and maintain wakefulness, and loss of orexin-producing neurons causes narcolepsy...
  18. Cui Y, Li M, Walton K, Sun K, Hanover J, Furth P, et al. The Stat3/5 locus encodes novel endoplasmic reticulum and helicase-like proteins that are preferentially expressed in normal and neoplastic mammary tissue. Genomics. 2001;78:129-34 pubmed
    ..Immunofluorescence studies demonstrated that LGP1 is located in the nuclear envelope and the endoplasmic reticulum. LGP2 is a cytoplasmic protein of 678 amino acids. ..
  19. Xie X, Crowder T, Yamanaka A, Morairty S, Lewinter R, Sakurai T, et al. GABA(B) receptor-mediated modulation of hypocretin/orexin neurones in mouse hypothalamus. J Physiol. 2006;574:399-414 pubmed
    Hypocretin/orexin (Hcrt) is a critical neurotransmitter for the maintenance of wakefulness and has been implicated in several other functions, including energy metabolism and reward...
  20. Sellayah D, Bharaj P, Sikder D. Orexin is required for brown adipose tissue development, differentiation, and function. Cell Metab. 2011;14:478-90 pubmed publisher
    b>Orexin (OX) neuropeptides stimulate feeding and arousal. Deficiency of orexin is implicated in narcolepsy, a disease associated with obesity, paradoxically in the face of reduced food intake...
  21. Zhang W, Sakurai T, Fukuda Y, Kuwaki T. Orexin neuron-mediated skeletal muscle vasodilation and shift of baroreflex during defense response in mice. Am J Physiol Regul Integr Comp Physiol. 2006;290:R1654-63 pubmed
    ..such as increases in arterial blood pressure (AP), heart rate (HR), and ventilation were attenuated in prepro-orexin knockout (ORX-KO) mice...
  22. Higuchi S, Usui A, Murasaki M, Matsushita S, Nishioka N, Yoshino A, et al. Plasma orexin-A is lower in patients with narcolepsy. Neurosci Lett. 2002;318:61-4 pubmed
    ..shown that in patients with narcolepsy, global reduction in the expression of orexins occurs due to the loss of orexin neurons in the hypothalamus...
  23. Plaza Zabala A, Flores A, Maldonado R, Berrendero F. Hypocretin/orexin signaling in the hypothalamic paraventricular nucleus is essential for the expression of nicotine withdrawal. Biol Psychiatry. 2012;71:214-23 pubmed publisher
    Hypocretin (orexin) signaling is involved in drug addiction. In this study, we investigated the role of these hypothalamic neuropeptides in nicotine withdrawal by using behavioral and neuroanatomical approaches...
  24. Burgess C, Oishi Y, Mochizuki T, Peever J, Scammell T. Amygdala lesions reduce cataplexy in orexin knock-out mice. J Neurosci. 2013;33:9734-42 pubmed publisher
    ..We then found that bilateral, excitotoxic lesions of the amygdala markedly reduced cataplexy in orexin knock-out mice, a model of narcolepsy...
  25. Mori T, Ito S, Kuwaki T, Yanagisawa M, Sakurai T, Sawaguchi T. Monoaminergic neuronal changes in orexin deficient mice. Neuropharmacology. 2010;58:826-32 pubmed publisher
    b>Orexin knockout (KO) mice and orexin/ataxin-3 mice (which have a different pathophysiological background in orexin deficiency) exhibit a phenotype that is similar to human narcolepsy...
  26. Muschamp J, Hollander J, Thompson J, Voren G, Hassinger L, Onvani S, et al. Hypocretin (orexin) facilitates reward by attenuating the antireward effects of its cotransmitter dynorphin in ventral tegmental area. Proc Natl Acad Sci U S A. 2014;111:E1648-55 pubmed publisher
    Hypocretin (orexin) and dynorphin are neuropeptides with opposing actions on motivated behavior. Orexin is implicated in states of arousal and reward, whereas dynorphin is implicated in depressive-like states...
  27. Georgescu D, Zachariou V, Barrot M, Mieda M, Willie J, Eisch A, et al. Involvement of the lateral hypothalamic peptide orexin in morphine dependence and withdrawal. J Neurosci. 2003;23:3106-11 pubmed
    ..The LH-specific peptide orexin (hypocretin) has been shown to be important in arousal and sleep regulation...
  28. Surendran S, Rady P, Szucs S, Michals Matalon K, Tyring S, Matalon R. High level of orexin A observed in the phenylketonuria mouse brain is due to the abnormal expression of prepro-orexin. Biochem Biophys Res Commun. 2004;317:522-6 pubmed
    ..Orexins regulate various functions including sleep and apetite. We recently reported increased amount of orexin A in the phenylketonuria (PKU) mouse brain...
  29. Soya S, Shoji H, Hasegawa E, Hondo M, Miyakawa T, Yanagisawa M, et al. Orexin receptor-1 in the locus coeruleus plays an important role in cue-dependent fear memory consolidation. J Neurosci. 2013;33:14549-57 pubmed publisher
    ..Since NA neurons in the LC (LC-NA neurons) abundantly express orexin receptor-1 (OX1R) and receive prominent innervation by orexin-producing neurons, we hypothesized that an OX1R-..
  30. Zhao T, Szabo N, Ma J, Luo L, Zhou X, Alvarez Bolado G. Genetic mapping of Foxb1-cell lineage shows migration from caudal diencephalon to telencephalon and lateral hypothalamus. Eur J Neurosci. 2008;28:1941-55 pubmed publisher
    ..The expanded neuroepithelium generates abundant neurons for the medial hypothalamus at the tuberal level. Finally, we have uncovered novel diencephalon-to-telencephalon migrations into septum, piriform cortex and amygdala. ..
  31. Gac L, Butterick T, Duffy C, Teske J, Perez Leighton C. Role of the non-opioid dynorphin peptide des-Tyr-dynorphin (DYN-A(2-17)) in food intake and physical activity, and its interaction with orexin-A. Peptides. 2016;76:14-8 pubmed publisher
    Food intake and physical activity are regulated by multiple neuropeptides, including orexin and dynorphin (DYN)...
  32. Li Y, van den Pol A. Differential target-dependent actions of coexpressed inhibitory dynorphin and excitatory hypocretin/orexin neuropeptides. J Neurosci. 2006;26:13037-47 pubmed
    The hypocretin/orexin arousal system plays a key role in maintaining an alert wake state. The hypocretin peptide is colocalized with an opioid peptide, dynorphin...
  33. Zhang W, Sunanaga J, Takahashi Y, Mori T, Sakurai T, Kanmura Y, et al. Orexin neurons are indispensable for stress-induced thermogenesis in mice. J Physiol. 2010;588:4117-29 pubmed publisher
    b>Orexin neurons contribute to cardiovascular, respiratory and analgesic components of the fight-or-flight response against stressors. Here, we examined whether the same is true for stress-induced hyperthermia...
  34. Joshi D, Singh S. Localization, expression and role of Orexin A and its receptor in testes of neonatal mice. Gen Comp Endocrinol. 2016;239:62-70 pubmed publisher
    b>Orexin A (OXA), a hypothalamic neuropeptide, and its receptor (OX1R) are primarily expressed in lateral hypothalamus and are involved in the control of various biological functions...
  35. Sokolowski K, Tran T, Esumi S, Kamal Y, Oboti L, Lischinsky J, et al. Molecular and behavioral profiling of Dbx1-derived neurons in the arcuate, lateral and ventromedial hypothalamic nuclei. Neural Dev. 2016;11:12 pubmed publisher
    ..Within these nuclei, Dbx1 (+) progenitors generate a large proportion of the Pmch-, Nesfatin-, Cart-, Hcrt-, Agrp- and ER?-expressing neuronal populations, and to a lesser extent the Pomc-, TH- and Aromatase-expressing ..
  36. Garcia Tornadú I, Diaz Torga G, Risso G, Silveyra P, Cataldi N, Ramirez M, et al. Hypothalamic orexin, OX1, alphaMSH, NPY and MCRs expression in dopaminergic D2R knockout mice. Neuropeptides. 2009;43:267-74 pubmed publisher
    ..We determined hypothalamic orexin precursor (PPO) expression, its receptor OX1, serum leptin levels, hypothalamic leptin receptor (OBR), circulating ..
  37. Lu G, Lee C, Chiou L. Orexin A induces bidirectional modulation of synaptic plasticity: Inhibiting long-term potentiation and preventing depotentiation. Neuropharmacology. 2016;107:168-180 pubmed publisher
    The orexin system consists of two peptides, orexin A and B and two receptors, OX1R and OX2R...
  38. Mochizuki T, Arrigoni E, Marcus J, Clark E, Yamamoto M, Honer M, et al. Orexin receptor 2 expression in the posterior hypothalamus rescues sleepiness in narcoleptic mice. Proc Natl Acad Sci U S A. 2011;108:4471-6 pubmed publisher
    Narcolepsy is caused by a loss of orexin/hypocretin signaling, resulting in chronic sleepiness, fragmented non-rapid eye movement sleep, and cataplexy...
  39. Kozlov S, Bogenpohl J, Howell M, Wevrick R, Panda S, Hogenesch J, et al. The imprinted gene Magel2 regulates normal circadian output. Nat Genet. 2007;39:1266-72 pubmed
    ..These changes are associated with reductions in food intake and male fertility. Orexin levels and orexin-positive neurons in the lateral hypothalamus are substantially reduced, suggesting that some of ..
  40. D Anna K, Gammie S. Hypocretin-1 dose-dependently modulates maternal behaviour in mice. J Neuroendocrinol. 2006;18:553-66 pubmed
    Increases in neuronal activity of hypocretin (HCRT), a peptide involved in arousal, and in HCRT-1 receptor mRNA expression have recently been identified in association with lactation...
  41. Mieda M, Hasegawa E, Kisanuki Y, Sinton C, Yanagisawa M, Sakurai T. Differential roles of orexin receptor-1 and -2 in the regulation of non-REM and REM sleep. J Neurosci. 2011;31:6518-26 pubmed publisher
    b>Orexin-A and orexin-B are hypothalamic neuropeptides that play critical roles in the maintenance of wakefulness...
  42. Irukayama Tomobe Y, Ogawa Y, Tominaga H, Ishikawa Y, Hosokawa N, Ambai S, et al. Nonpeptide orexin type-2 receptor agonist ameliorates narcolepsy-cataplexy symptoms in mouse models. Proc Natl Acad Sci U S A. 2017;114:5731-5736 pubmed publisher
    Narcolepsy-cataplexy is a debilitating disorder of sleep/wakefulness caused by a loss of orexin-producing neurons in the lateroposterior hypothalamus...
  43. Hondo M, Nagai K, Ohno K, Kisanuki Y, Willie J, Watanabe T, et al. Histamine-1 receptor is not required as a downstream effector of orexin-2 receptor in maintenance of basal sleep/wake states. Acta Physiol (Oxf). 2010;198:287-94 pubmed publisher
    The effect of orexin on wakefulness has been suggested to be largely mediated by activation of histaminergic neurones in the tuberomammillary nucleus (TMN) via orexin receptor-2 (OX(2)R)...
  44. Hasegawa E, Maejima T, Yoshida T, Masseck O, Herlitze S, Yoshioka M, et al. Serotonin neurons in the dorsal raphe mediate the anticataplectic action of orexin neurons by reducing amygdala activity. Proc Natl Acad Sci U S A. 2017;114:E3526-E3535 pubmed publisher
    Narcolepsy is a sleep disorder caused by the loss of orexin (hypocretin)-producing neurons and marked by excessive daytime sleepiness and a sudden weakening of muscle tone, or cataplexy, often triggered by strong emotions...
  45. Plaza Zabala A, Martín García E, de Lecea L, Maldonado R, Berrendero F. Hypocretins regulate the anxiogenic-like effects of nicotine and induce reinstatement of nicotine-seeking behavior. J Neurosci. 2010;30:2300-10 pubmed publisher
    ..8 mg/kg, s.c.) administration. Intracerebroventricular infusion of hypocretin-1 (Hcrt-1) (0.75 nmol/1 mul) or footshock stress reinstated a previously extinguished nicotine-seeking behavior...
  46. Mochizuki T, Klerman E, Sakurai T, Scammell T. Elevated body temperature during sleep in orexin knockout mice. Am J Physiol Regul Integr Comp Physiol. 2006;291:R533-40 pubmed
    ..To determine the relative roles of these factors, we examined Tb in orexin knockout (KO) mice, which have a narcolepsy-like phenotype with severe sleep-wake fragmentation...
  47. Wang Z, Liu S, Kakizaki M, Hirose Y, Ishikawa Y, Funato H, et al. Orexin/hypocretin activates mTOR complex 1 (mTORC1) via an Erk/Akt-independent and calcium-stimulated lysosome v-ATPase pathway. J Biol Chem. 2014;289:31950-9 pubmed publisher
    The lack of the neuropeptide orexin, also known as hypocretin, results in narcolepsy, a chronic sleep disorder characterized by frequent sleep/cataplexy attacks and rapid eye movement sleep abnormalities...
  48. Furutani N, Hondo M, Kageyama H, Tsujino N, Mieda M, Yanagisawa M, et al. Neurotensin co-expressed in orexin-producing neurons in the lateral hypothalamus plays an important role in regulation of sleep/wakefulness states. PLoS ONE. 2013;8:e62391 pubmed publisher
    Both orexin and neurotensin are expressed in the lateral hypothalamic area (LHA) and have been implicated in the regulation of feeding, motor activity and the reward system...
  49. Kaur S, Thankachan S, Begum S, Liu M, Blanco Centurion C, Shiromani P. Hypocretin-2 saporin lesions of the ventrolateral periaquaductal gray (vlPAG) increase REM sleep in hypocretin knockout mice. PLoS ONE. 2009;4:e6346 pubmed publisher
    Ten years ago the sleep disorder narcolepsy was linked to the neuropeptide hypocretin (HCRT), also known as orexin. This disorder is characterized by excessive day time sleepiness, inappropriate triggering of rapid-eye movement (REM) ..
  50. Oishi Y, Williams R, Agostinelli L, Arrigoni E, Fuller P, Mochizuki T, et al. Role of the medial prefrontal cortex in cataplexy. J Neurosci. 2013;33:9743-51 pubmed publisher
    ..Narcolepsy with cataplexy is caused by a loss of orexin (also known as hypocretin) signaling, but almost nothing is known about the neural mechanisms through which ..
  51. Tsunematsu T, Tabuchi S, Tanaka K, Boyden E, Tominaga M, Yamanaka A. Long-lasting silencing of orexin/hypocretin neurons using archaerhodopsin induces slow-wave sleep in mice. Behav Brain Res. 2013;255:64-74 pubmed publisher
    b>Orexin/hypocretin neurons have a crucial role in the regulation of sleep and wakefulness...
  52. Snow M, Fraigne J, Thibault Messier G, Chuen V, Thomasian A, Horner R, et al. GABA Cells in the Central Nucleus of the Amygdala Promote Cataplexy. J Neurosci. 2017;37:4007-4022 pubmed publisher
    ..and chemogenetic strategies to target and manipulate CeA activity selectively in narcoleptic (orexin-/-) mice to determine its functional role in controlling cataplexy...
  53. Zhang X, Yang H, Zhang Q, Wang Z, Wang D. Increased feeding and food hoarding following food deprivation are associated with activation of dopamine and orexin neurons in male Brandt's voles. PLoS ONE. 2011;6:e26408 pubmed publisher
    ..Fos-ir in the ventral tegmental area (VTA), whereas both FD and feeding induced an increase in the percentage of orexin-ir cells that co-expressed Fos-ir in the lateral hypothalamus (LH)...
  54. Petersen A, Gil J, Maat Schieman M, Björkqvist M, Tanila H, Araújo I, et al. Orexin loss in Huntington's disease. Hum Mol Genet. 2005;14:39-47 pubmed
    ..We describe for the first time a dramatic atrophy and loss of orexin neurons in the lateral hypothalamus of R6/2 mice...
  55. Shiuchi T, Haque M, Okamoto S, Inoue T, Kageyama H, Lee S, et al. Hypothalamic orexin stimulates feeding-associated glucose utilization in skeletal muscle via sympathetic nervous system. Cell Metab. 2009;10:466-80 pubmed publisher
    Hypothalamic neurons containing orexin (hypocretin) are activated during motivated behaviors and active waking...
  56. Diniz Behn C, Klerman E, Mochizuki T, Lin S, Scammell T. Abnormal sleep/wake dynamics in orexin knockout mice. Sleep. 2010;33:297-306 pubmed
    Narcolepsy with cataplexy is caused by a loss of orexin (hypocretin) signaling, but the physiologic mechanisms that result in poor maintenance of wakefulness and fragmented sleep remain unknown...
  57. Miyata K, Kuwaki T, Ootsuka Y. The integrated ultradian organization of behavior and physiology in mice and the contribution of orexin to the ultradian patterning. Neuroscience. 2016;334:119-133 pubmed publisher
    ..We also incorporated the same recording in prepro-orexin knockout (ORX-KO) mice to reveal the role of orexin in the brain mechanisms underlying ultradian patterning...
  58. McGregor R, Wu M, Barber G, Ramanathan L, Siegel J. Highly specific role of hypocretin (orexin) neurons: differential activation as a function of diurnal phase, operant reinforcement versus operant avoidance and light level. J Neurosci. 2011;31:15455-67 pubmed publisher
    Hypocretin (Hcrt) cell loss is responsible for narcolepsy, but Hcrt's role in normal behavior is unclear. We found that Hcrt knock-out mice were unable to work for food or water reward during the light phase...
  59. de Miguel M, Burrell M. Immunocytochemical detection of orexin A in endocrine cells of the developing mouse gut. J Histochem Cytochem. 2002;50:63-9 pubmed
    ..Recently orexin A and its receptor have also been reported in neurons and endocrine cells of the gastrointestinal tract...
  60. Silvani A, Bastianini S, Berteotti C, Lo Martire V, Zoccoli G. Control of cardiovascular variability during undisturbed wake-sleep behavior in hypocretin-deficient mice. Am J Physiol Regul Integr Comp Physiol. 2012;302:R958-64 pubmed publisher
    ..These mechanisms may involve hypocretin (HCRT)/orexin signaling...
  61. Fujiki N, Yoshida Y, Zhang S, Sakurai T, Yanagisawa M, Nishino S. Sex difference in body weight gain and leptin signaling in hypocretin/orexin deficient mouse models. Peptides. 2006;27:2326-31 pubmed
    ..In the current study, using two hypocretin/orexin deficient narcoleptic mouse models (i.e...
  62. Yang L, Zou B, Xiong X, Pascual C, Xie J, Malik A, et al. Hypocretin/orexin neurons contribute to hippocampus-dependent social memory and synaptic plasticity in mice. J Neurosci. 2013;33:5275-84 pubmed publisher
    Hypocretin/orexin (Hcrt)-producing neurons in the lateral hypothalamus project throughout the brain, including to the hippocampus, where Hcrt receptors are widely expressed...
  63. Hasegawa E, Yanagisawa M, Sakurai T, Mieda M. Orexin neurons suppress narcolepsy via 2 distinct efferent pathways. J Clin Invest. 2014;124:604-16 pubmed publisher
    The loss of orexin neurons in humans is associated with the sleep disorder narcolepsy, which is characterized by excessive daytime sleepiness and cataplexy...
  64. Honda M, Eriksson K, Zhang S, Tanaka S, Lin L, Salehi A, et al. IGFBP3 colocalizes with and regulates hypocretin (orexin). PLoS ONE. 2009;4:e4254 pubmed publisher
    The sleep disorder narcolepsy is caused by a vast reduction in neurons producing the hypocretin (orexin) neuropeptides...
  65. Mochizuki T, Crocker A, McCormack S, Yanagisawa M, Sakurai T, Scammell T. Behavioral state instability in orexin knock-out mice. J Neurosci. 2004;24:6291-300 pubmed
    Narcolepsy is caused by a lack of orexin (hypocretin), but the physiologic process that underlies the sleepiness of narcolepsy is unknown...
  66. Palotai M, Telegdy G, Jászberényi M. Orexin A-induced anxiety-like behavior is mediated through GABA-ergic, ?- and ?-adrenergic neurotransmissions in mice. Peptides. 2014;57:129-34 pubmed publisher
    ..Several studies provide biochemical and behavioral evidence about the anxiogenic action of orexin A. However, we have little evidence about the underlying neuromodulation...
  67. Collin G, Maddatu T, Sen S, Naggert J. Genetic modifiers interact with Cpe(fat) to affect body weight, adiposity, and hyperglycemia. Physiol Genomics. 2005;22:182-90 pubmed
  68. Matsuo E, Mochizuki A, Nakayama K, Nakamura S, Yamamoto T, Shioda S, et al. Decreased intake of sucrose solutions in orexin knockout mice. J Mol Neurosci. 2011;43:217-24 pubmed publisher
    ..Recent studies have shown that intracerebroventricular administration of orexin-A increases intake of sweet-tasting solution...
  69. Adeghate E, Fernandez Cabezudo M, Hameed R, El Hasasna H, El Wasila M, Abbas T, et al. Orexin-1 receptor co-localizes with pancreatic hormones in islet cells and modulates the outcome of streptozotocin-induced diabetes mellitus. PLoS ONE. 2010;5:e8587 pubmed publisher
    ..This function is deranged in diabetes mellitus. This study examined the pattern of distribution of orexin-1 receptor (OX1R) in the endocrine cells of the pancreas of normal and diabetic Wistar (a model of type 1 diabetes)..
  70. Anaclet C, Parmentier R, Ouk K, Guidon G, Buda C, Sastre J, et al. Orexin/hypocretin and histamine: distinct roles in the control of wakefulness demonstrated using knock-out mouse models. J Neurosci. 2009;29:14423-38 pubmed publisher
    To determine the respective role played by orexin/hypocretin and histamine (HA) neurons in maintaining wakefulness (W), we characterized the behavioral and sleep-wake phenotypes of orexin (Ox) knock-out (-/-) mice and compared them with ..
  71. Terada J, Nakamura A, Zhang W, Yanagisawa M, Kuriyama T, Fukuda Y, et al. Ventilatory long-term facilitation in mice can be observed during both sleep and wake periods and depends on orexin. J Appl Physiol (1985). 2008;104:499-507 pubmed
    ..Raphe nuclei, which modulate several physiological functions through serotonin, receive dense projections from orexin-containing neurons in the hypothalamus...
  72. González J, Iordanidou P, Strom M, Adamantidis A, Burdakov D. Awake dynamics and brain-wide direct inputs of hypothalamic MCH and orexin networks. Nat Commun. 2016;7:11395 pubmed publisher
    The lateral hypothalamus (LH) controls energy balance. LH melanin-concentrating-hormone (MCH) and orexin/hypocretin (OH) neurons mediate energy accumulation and expenditure, respectively...
  73. Yamamoto Y, Ueta Y, Date Y, Nakazato M, Hara Y, Serino R, et al. Down regulation of the prepro-orexin gene expression in genetically obese mice. Brain Res Mol Brain Res. 1999;65:14-22 pubmed
    The gene expression of prepro-orexin, the precursor of orexin-A and orexin-B which are hypothalamic pepetides that are associated with feeding behavior, were examined in control (C57B1/6J) and obese (ob/ob and db/db) mice using in situ ..
  74. Burgess C, Peever J. A noradrenergic mechanism functions to couple motor behavior with arousal state. Curr Biol. 2013;23:1719-25 pubmed publisher
    ..Cataplexy is caused by loss of hypocretin (orexin) cells, but it is unknown how this loss triggers motor inactivity during cataplexy...
  75. Tsuneki H, Nagata T, Fujita M, Kon K, Wu N, Takatsuki M, et al. Nighttime Administration of Nicotine Improves Hepatic Glucose Metabolism via the Hypothalamic Orexin System in Mice. Endocrinology. 2016;157:195-206 pubmed publisher
    ..in drinking water, which mainly occurred during the nighttime active period, enhanced daily hypothalamic prepro-orexin gene expression and reduced hyperglycemia in type 2 diabetic db/db mice without affecting body weight, body fat ..
  76. Joshi D, Sarkar D, Singh S. Decreased expression of orexin 1 receptor in adult mice testes during alloxan-induced diabetes mellitus perturbs testicular steroidogenesis and glucose homeostasis. Biochem Biophys Res Commun. 2017;490:1346-1354 pubmed publisher
    ..Results show involvement of orexin A (OXA) and its receptor (OX1R) in regulation of steroidogenesis and glucose homeostasis in adult mice testis...
  77. Wei W, Motoike T, Krzeszinski J, Jin Z, Xie X, Dechow P, et al. Orexin regulates bone remodeling via a dominant positive central action and a subordinate negative peripheral action. Cell Metab. 2014;19:927-40 pubmed publisher
    b>Orexin neuropeptides promote arousal, appetite, reward, and energy expenditure. However, whether orexin affects bone mass accrual is unknown...
  78. Tanaka S, Kodama T, Nonaka T, Toyoda H, Arai M, Fukazawa M, et al. Transcriptional regulation of the hypocretin/orexin gene by NR6A1. Biochem Biophys Res Commun. 2010;403:178-83 pubmed publisher
    The hypocretin (also known as orexin) neuropeptide system coordinates the regulation of various physiological processes. A reduction in Nr6a1 expression was observed in hypocretin neuron-ablated transgenic mice...
  79. Tsuneki H, Kon K, Ito H, Yamazaki M, Takahara S, Toyooka N, et al. Timed Inhibition of Orexin System by Suvorexant Improved Sleep and Glucose Metabolism in Type 2 Diabetic db/db Mice. Endocrinology. 2016;157:4146-4157 pubmed
    ..To investigate this possibility, we here examined the effects of suvorexant, an antiinsomnia drug targeting the orexin system, on sleep and glucose metabolism in type 2 diabetic mice...
  80. Siegel J. Narcolepsy: a key role for hypocretins (orexins). Cell. 1999;98:409-12 pubmed
  81. Arendt D, Ronan P, Oliver K, Callahan L, Summers T, Summers C. Depressive behavior and activation of the orexin/hypocretin system. Behav Neurosci. 2013;127:86-94 pubmed publisher
    ..Animals that displayed relatively more depressive behavior had lower hippocampal expression of Orexin A (OrxA). In the amygdala, there was a curvilinear relationship between OrxA and FST performance...