• We suggested a pivotal role for endocannabinoids in food reward processing within the lateral hypothalamus, and for orexin neurons to integrate endocrine signals with food reinforcement and hedonic eating. (frontiersin.org)
  • In addition, the role played by different stressors in the reinstatement of preference for palatable food and food-seeking behavior is also considered in the light of endocannabinoid production, activation of orexin receptors and disinhibition of dopamine neurons. (frontiersin.org)
  • Increase of energy accumulation elicits leptin release and simultaneous inhibition of orexigenic neurons expressing neuropeptide Y (NPY) and agouti-related peptide (AgRP), as well as activation of the anorexigenic proopiomelanocortin (POMC) neurons within the hypothalamic arcuate nucleus (ARC). (frontiersin.org)
  • Moreover, orexins have been reported to greatly influence gonadotropin-releasing hormone neurons and their secretions to regulate reproductive functions via modulation of the hypothalamic-pituitary-gonadal axis. (researchgate.net)
  • Orexins/hypocretins are recently discovered neuropeptides synthetized mainly by neurons located in the posterolateral hypothalamus. (nel.edu)
  • Moreover, orexin neurons, by acting on OxR1 in the LC, play a role in the diurnal gating of REM sleep. (nih.gov)
  • Prof. Shoenfeld discovered that a group of researchers from the Sleep Control Project at the Tokyo Metropolitan Institute of Psychiatry in Japan had published a study on an autoantibody presence attacking tribbles, small granules in our brains containing regulatory orexin neurons, which maintain the balance between sleep and wakefulness in the brain. (sciencedaily.com)
  • Neuropeptide Y/agouti-related protein- and proopiomelanocortin-producing neurons in the hypothalamic arcuate nucleus primarily sense the body energy state. (nature.com)
  • 4 In the ARC, there are two distinct neuronal populations: one group of neurons produces the orexigenic neuropeptides neuropeptide Y (NPY) and agouti-related peptide (AgRP), whereas the other subset of neurons expresses the anorexigenic neuropeptides proopiomelanocortin (POMC), and cocaine- and amphetamine-regulated transcript. (nature.com)
  • The anorexigenic neuropeptide α-melanocyte-stimulating hormone (α-MSH) is produced by posttranscriptional processing of POMC and is released from the presynaptic terminals of POMC neurons. (nature.com)
  • Both orexin-A and orexin-B depolarized the histaminergic tuberomammillary neurons and increased their firing rate via an action on postsynaptic receptors. (jneurosci.org)
  • In a single-cell RT-PCR study using primers for the two orexin receptors, we found that most tuberomammillary neurons express both receptors and that the expression of the orexin-2 receptor is stronger than that of the orexin-1 receptor. (jneurosci.org)
  • Immunocytochemical studies show that the histamine and orexin neurons are often located very close to each other. (jneurosci.org)
  • The contacts between these two types of neurons seem to be reciprocal, because the orexin neurons are heavily innervated by histaminergic axons. (jneurosci.org)
  • The sleep disorder narcolepsy is considered to be a neurodegenerative disease because there is a massive progressive loss of neurons containing the neuropeptide orexin. (uni-marburg.de)
  • The postulated pathophysiology of human narcolepsy is mimicked very closely in a transgenic mouse model called orexin/ataxin-3 mouse, in which orexin-containing neurons are ablated progressively by specific overexpression of a truncated cytotoxic ataxin-3 gene product under the orexin-promoter. (uni-marburg.de)
  • By triple staining we could show that the proportion of newly born neurons relative to the total number of newly built cells in the HC was significantly higher with 90 % in the orexin-ataxin group compared to 83 % in the control group. (uni-marburg.de)
  • Also the rate of differentiation into a dopaminergic phenotype of the newly born neurons in the periglomerular zone of the OB was not significantly changed with 93 % in the orexin/ataxin-3 mice compared to 91 % in the WT mice. (uni-marburg.de)
  • Orexin interacts with several wake-promoting neuronal groups, such as the histaminergic neurons of the tuberomammilary nucleus and the noradrenergic neurons of the locus coeruleus. (proteopedia.org)
  • Therefore, it can be concluded that when Orexin neurons are stimulated the possibility of transitioning to a state of wakefulness increases. (proteopedia.org)
  • However, if Orexin neurons are inhibited the probability of transitioning to sleeping state increases. (proteopedia.org)
  • The hypothalamus has emerged as an important area of pathology with selective loss of neurons expressing the neuropeptides orexin (hypocretin), oxytocin and vasopressin in human postmortem HD tissue. (lu.se)
  • Pacemaker neuron-dependent activity rhythms were also found in a second circadian output pathway controlled by DH44 neuropeptide-expressing neurons. (sdbonline.org)
  • Narcoleptic patients are believed to suffer from selective destruction of Hypothalamic neurons, which are responsible for producing Orexin, also termed Hypocretin (HCRT), a neurotransmitter involved in regulating sleep-wake states. (substack.com)
  • We have identified that a group of SCN neurons that show a neuropeptide known as neuromedin S (NMS) is both essential and adequate for the control of circadian rhythms. (clinicalresearchsociety.org)
  • Orexin neurons produce a small protein, the orexin neuropeptide, known to be involved in promoting wakefulness. (ohsu.edu)
  • Orexin neurons are located in the hypothalamus, an area lacking a blood brain barrier. (ohsu.edu)
  • An orexin receptor antagonist, or orexin antagonist, is a drug that inhibits the effect of orexin by acting as a receptor antagonist of one or both of the orexin receptors, OX1 and OX2. (wikipedia.org)
  • The orexin receptors (orexin 1R and orexin 2R) belong to the Family of G-protein coupled receptors. (researchgate.net)
  • The primary function of the orexin system, i.e. the orexins, their receptors and associated neuronal circuitries, perhaps is to increase spontaneous physical activity and food intake, thereby promoting an increase in energy expenditure. (researchgate.net)
  • Contextual generalization of social stress learning is modulated by orexin receptors in basolateral amygdala, 1-12. (usd.edu)
  • DAYVIGO is a dual orexin receptor antagonist that inhibits orexin neurotransmission regulating sleep-wake rhythm by binding competitively to the two subtypes of orexin receptors (OX1R and OX2R). (eisai.com)
  • DAYVIGO binds to orexin receptors OX1R and OX2R and acts as a competitive antagonist with stronger inhibition effect on OX2R, which suppresses both REM and non-REM sleep drive, such that DAYVIGO may provide faster sleep onset and better sleep maintenance to patients. (eisai.com)
  • DAYVIGO is Eisai's in-house discovered and developed small molecule that binds to orexin receptors, OX1R and OX2R, and acts as a competitive antagonist (IC 50 values of 6.1 nM and 2.6 nM, respectively). (eisai.com)
  • The mechanism of action of DAYVIGO in the treatment of insomnia is presumed to be through antagonism of orexin receptors. (eisai.com)
  • Blocking the binding of wake-promoting neuropeptides orexin to receptors OX1R and OX2R is thought to suppress wake drive (Ki values of 8.1 nM and 0.48 nM, respectively). (eisai.com)
  • Astyanax mexicanus have OX2R receptors that are more sensitive, and have an increased blood level of orexin . (lesswrong.com)
  • Both Orexin-peptides consist of two amphipathic α-helixes, which have similar properties to the N-terminal α-helixes found on Orexin receptors. (proteopedia.org)
  • Orexin-A can be described as a non-subtype-selective neuropeptide that is capable of binding to either OX1R and OX2R, the two possible Orexin receptors, with roughly equal affinities. (proteopedia.org)
  • Orexin receptors produce neuroexcitation through postsynaptic depolarization by activating non-selective cation channels, inhibiting K+ channels, and activating Na+/Ca2+ exchange. (proteopedia.org)
  • Both Orexin receptors have been shown to couple strongly with Ca2+ ion elevations and phospholipase C. Low concentrations of Orexin causes OX1R stimulation, activating a Ca2+ influx [3] . (proteopedia.org)
  • While some signalling mechanisms have been proposed for individual recombinant orexin receptors in generic mammalian cell types, it is clear that the peripheral effects of orexin are spatially and temporally complex. (warwick.ac.uk)
  • Interestingly, G-protein-coupled Orexin receptors are found in the Pineal Gland and affect Melatonin secretion. (substack.com)
  • In Orexin/Hypocretin 21 Years On: Pharmacology, Physiology and Drug Discovery , 1-20. (usd.edu)
  • VSI: Orexin/Hypocretin Beijing: Medicine in Drug Discovery/Elsevier, 2020. (usd.edu)
  • The hypothalamic orexin (hypocretin) neuropeptides are associated with the regulation of sleep and feeding, and disturbances in orexinergic neurotransmission lead to a narcoleptic phenotype. (jneurosci.org)
  • Hypocretin is an alternative name in the literature for orexin, hypocretin-1 for orexin A, and hypocretin-1 for orexin B. (lesswrong.com)
  • Orexin/hypocretin signaling at the orexin 1 receptor regulates cue-elicited cocaine-seeking. (tamu.edu)
  • The orexin/hypocretin system has recently been implicated in reward-processing and addiction. (tamu.edu)
  • Orexin (Hypocretin) is a key Neuropeptide involved in Narcolepsy. (substack.com)
  • In April 2023, the UK government admitted that Hypocretin = Orexin is the key to Narcolepsy caused by Pandemrix, but still falselly claimed the mechanism is unknown. (substack.com)
  • The orexin neuropeptide signaling system plays a role in wakefulness. (eisai.com)
  • Fragmented sleep is caused by the instability of behavioral state regulation due to the lack of Orexin lowering the thresholds required to transition between sleep and wakefulness. (proteopedia.org)
  • Daridorexant is a dual orexin receptor antagonist that blocks the binding of the wake-promoting orexin neuropeptides, and is thought to turn down overactive wakefulness, as opposed to treatments that generally sedate the brain. (fhea.com)
  • Orexin is a neuropeptide that regulates arousal, wakefulness, and appetite. (supermindhacker.com)
  • Prof. Yanagisawa, identified that one more neuropeptide known as orexin controls sleep/wakefulness. (clinicalresearchsociety.org)
  • Modafinil also affects the levels of orexin, a neuropeptide that regulates wakefulness and appetite. (gymposts.com)
  • Numerous Phase II and Phase III clinical trials are under way that replace or bypass the function of the orexin neuropeptide to treat narcolepsy, a disorder characterized by disrupted wakefulness and impaired orexin neuron signaling. (ohsu.edu)
  • Narcolepsy, a neurological disorder caused by orexin deficiency, is a contraindication to the use of orexin antagonists. (wikipedia.org)
  • In patients and animals that develop narcolepsy, we have seen an evident depletion of orexin in the brain, and therefore a lack of balance, and later attacks of narcolepsy," said Prof. Shoenfeld. (sciencedaily.com)
  • whereas a disrupted orexin system leads to narcolepsy. (jneurosci.org)
  • Several Nobel watchers have suggested this year's prize could go to research into narcolepsy and the discovery of orexin, a neuropeptide that helps regulate sleep. (medicalxpress.com)
  • Low amounts of Orexin and mutations of the OX2R gene (HCRTR2) have been linked to the development of narcolepsy, a sleep disorder characterized by excessive daytime sleepiness, cataplexy, sleep paralysis, and hypnagogic hallucinations. (proteopedia.org)
  • The results, produced by providing orexin-A neuropeptides to counteract fatigue in rats and mice, suggests that narcolepsy drugs in development, including those in advanced clinical trials, may prove beneficial to cancer patients. (ohsu.edu)
  • Lemborexant, an orexin receptor antagonist sedative-hypnotic: Is it useful for insomnia in psychiatric disorders? (wikipedia.org)
  • Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, "Eisai") announced today that its Hong Kong subsidiary Eisai (Hong Kong) Co., Ltd. has obtained approval for the in-house-discovered and developed orexin receptor antagonist DAYVIGO ® (generic name: lemborexant) for the treatment of adults with insomnia, characterized by difficulties with sleep onset and/or sleep maintenance. (eisai.com)
  • Daridorexant is a dual orexin receptor antagonist for the treatment of insomnia. (springer.com)
  • We examined the involvement of the orexin system in cue-induced reinstatement of extinguished cocaine-seeking by administering the orexin 1 receptor antagonist SB-334867 (SB) or the orexin 2 receptor antagonist 4-pyridylmethyl (S)-tert-leucyl 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (4PT) prior to reinstatement testing. (tamu.edu)
  • It has been reported that the peptides such as orexins, neuropeptide Y (NPY) and leptin may play an important role in the regul. (nel.edu)
  • and the orexin peptides have been implicated in physiological roles similar to those of HA. (jneurosci.org)
  • Blood samples were collected at months 0, 4, and 8 to look at insulin, lipids (e.g., triglycerides, total cholesterol, free fatty acid and low-density lipoprotein cholesterol), and brain-gut peptides (including GLP-1, neuropeptide Y, and orexin A). Gene sequencing was used to detect any changes to the gut microbiota. (restorativemedicine.org)
  • Orexin-A binds to both OX1R and OX2R with a high affinity, whereas orexin-B binds only to OX2R with a similar high affinity. (lesswrong.com)
  • However, Orexin-B binds to OX2R with an affinity 10 times greater than its affinity for OX1R [2] . (proteopedia.org)
  • Orexin receptor antagonists are not currently used as first-line treatments for insomnia due to cost and concerns about possible misuse liability. (wikipedia.org)
  • Rates of somnolence or fatigue with orexin receptor antagonists in clinical trials were 7% (vs. 3% with placebo) for suvorexant 15 to 20 mg, 7 to 10% (vs. 1.3% for placebo) for lemborexant 5 to 10 mg, and 5 to 6% (vs. 4% with placebo) for daridorexant 25 to 50 mg. (wikipedia.org)
  • The elimination half-lives of clinically used orexin receptor antagonists are 12 hours for suvorexant, about 17 to 19 hours ("effective" half-life) or 55 hours (terminal elimination half-life) for lemborexant, and 6 to 10 hours for daridorexant. (wikipedia.org)
  • The elimination half-lives of investigational orexin receptor antagonists are 2 to 3 hours for seltorexant and about 1.5 to 3 hours for vornorexant. (wikipedia.org)
  • All three marketed orexin antagonists do not need to be dose adjusted in patients with reduced renal function, as the pharmacokinetic profiles of these medications are not significantly affected. (wikipedia.org)
  • Comparative Pharmacology of the 3 Marketed Dual Orexin Antagonists-Daridorexant, Lemborexant, and Suvorexant-Part 2. (wikipedia.org)
  • Analysis using signalling and MAPK inhibitors as well as receptor-specific antagonists determined the precise mediators of the orexin response in these cells. (warwick.ac.uk)
  • Orexins (or hypocretins) are hypothalamic neuropeptides with a multitude of physiological functions. (researchgate.net)
  • Hypocretins, also called Orexins, are hypothalamic neuropeptides that serve important functions in the regulation of an individual's sleep/wake cycle, homeostatic systems such as thermoregulation, appetite, and reward processing [1] . (proteopedia.org)
  • Consequently narcoleptic patients have very low cerebrospinal fluid levels of orexin. (uni-marburg.de)
  • By increasing the levels of orexin, modafinil may suppress appetite and lead to weight loss. (gymposts.com)
  • Thus, the lateral hypothalamus-ventral tegmental area-nucleus accumbens neural circuitry is reexamined in order to interrogate the functional interplay between ghrelin, dopamine, orexin, and endocannabinoid signaling. (frontiersin.org)
  • Finally, type-1 cannabinoid receptor-dependent inhibition of GABA-ergic release and relapse to reward-associated stimuli is linked to ghrelin and orexin signaling in the lateral hypothalamus-ventral tegmental area-nucleus accumbens network to highlight its pathological potential for food addiction-like behavior. (frontiersin.org)
  • After establishing the TBI model, the hypothalamus region was covered with LIFUS radiation, and an orexin receptor 1 (OXR1) antagonist (SB334867) was injected intraperitoneally. (aging-us.com)
  • Orexin is produced in the hypothalamus, a region of the brain that controls hunger and satiety. (gymposts.com)
  • precursor, prepro-orexin (PPO). (researchgate.net)
  • The DEC2 gene produces prepro-orexin, which is 131 amino acids long. (lesswrong.com)
  • People with the DEC2-P384R mutation produce more prepro-orexin and have a reduced need for sleep. (lesswrong.com)
  • From prepro-orexin our body generates orexin A, which is 33 amino acids long, and orexin B, which is 28 amino acids long. (lesswrong.com)
  • I didn't find information on whether or not prepro-orexin passes the barrier, but it likely doesn't given its size. (lesswrong.com)
  • The literature is sometimes unclear when they use the term orexin about whether the author means prepro-orexin, orexin A, and orexin B or a mix of them. (lesswrong.com)
  • They occur in two known forms, namely, orexin A and orexin B with a common precursor, preproorexin. (researchgate.net)
  • Results: We found a significantly higher proliferation of stem/precursor cells in the orexin/ataxin-3 mice in both neurogenic regions, the SGZ and the SVZ. (uni-marburg.de)
  • Conclusion: In the absence of orexin in the adult mouse brain, the proliferation of adult neural stem/precursor cells was increased, the survival rate was significantly increased in the granular zone of the OB and a consistent not significant trend was seen in the HC. (uni-marburg.de)
  • Fatigue brought on by chemotherapy may be reversed with orexin, a brain protein that regulates arousal and sleep, according to a study led by an investigator with the Knight Cancer Institute at Oregon Health & Science University (OHSU). (ohsu.edu)
  • While the mode of action of modafinil is mainly unclear, it is postulated that modafinil upregulates the production of orexin. (supermindhacker.com)
  • Orexin inhibitors (eg, lemborexant, suvorexant) are options for patients with difficulties of sleep onset and/or sleep maintenance. (medscape.com)
  • Effects of leptin and neuropeptide Y (NPY) on hormones release in female rats. (nel.edu)
  • Borowiec M, Wasilewska-Dziubiñska E, Chmielowska M, Woliñska-Witort E, Baranowska B. Effects of leptin and neuropeptide Y (NPY) on hormones release in female rats. (nel.edu)
  • Orexin A is highly conserved and has the same molecular structure in humans, mice, rats, and cows, while human orexin B differs from rodent orexin B. While orexin B doesn't cross the blood-brain barrier, orexin A does. (lesswrong.com)
  • Orexins A and B (ORA and ORB) are neuropeptide hormones found throughout the central nervous system and periphery. (warwick.ac.uk)
  • Recent research also has thrown lights upon a significant role of orexins, especially orexin A, in regulation of male reproductive functions owing to their receptor expressions in vital testicular cells, such as Leydig cells, Sertoli cells as well as spermatozoa at different developmental stages, even in the epididymis and penis. (researchgate.net)
  • Aim: We aimed to study the possible role of the protein orexin in the regulation of adult neurogenesis in the orexin/ataxin-3 mouse. (uni-marburg.de)
  • DAYVIGO acts on the orexin neurotransmitter system and is believed to facilitate sleep onset, sleep maintenance, and wake by regulating sleep-wake rhythm. (eisai.com)
  • In contrast, neuronal populations expressing orexin, oxytocin, vasopressin as well as tyrosine hydroxylase in the A13 area are resistant to QA-induced toxicity. (lu.se)
  • We demonstrate that the R6/2 transgenic mouse model expressing a short fragment of mutant HTT displays hypothalamic neuropathology with discrete loss of the neuronal populations expressing orexin, MCH, CART, and orexin at 12 weeks of age. (lu.se)
  • There was no effect of hypothalamic injections of QA on the neuronal populations expressing orexin, MCH, CART or oxytocin in neither HD mouse model. (lu.se)
  • Since narcoleptic individuals tends to fall asleep during the day, but wake up repeatedly at night, it is likely that Orexin functions as a way to stabilize the transition between sleep and wake states, as well as causing the transition between the states. (proteopedia.org)
  • The physiological role of orexins. (nel.edu)
  • These data Suggest multiple roles for orexin-mediated MAPK activation in an adrenal cell-line, this complexity may help to explain the diverse biological actions of orexins with wide-ranging consequences for Our understanding of the mechanisms initiated by these steroidogenic molecules. (warwick.ac.uk)
  • Effects were broadly comparable for both orexin sub-types ORA and ORB and although most of the effects were transmitted through the orexin receptor-1 subtype, we did observe a role for orexin receptor-2-mediated activation of both ERK1/2 and p38. (warwick.ac.uk)
  • The role of neuropeptides in the disturbed control of appetite and hormone secretion in eating disorders. (nel.edu)
  • It has been reported that neuropeptides may play a role in the control of appetite and in the mechanism of hormone release. (nel.edu)
  • Baranowska B, Wolinska-Witort E, Wasilewska-Dziubinska E, Roguski K, Martynska L, Chmielowska M. The role of neuropeptides in the disturbed control of appetite and hormone secretion in eating disorders. (nel.edu)
  • He and his co-workers have since determined several pathways engaged in the management of appetite and blood pressure, plus other neuropeptides that help manage functions like metabolism, stress and feelings. (clinicalresearchsociety.org)
  • Here we used small interfering RNAs (siRNAs) to test the role of LC orexin type 1 receptor (OxR1) in sleep-wake control. (nih.gov)
  • Chemotherapy-induced fatigue was reversed when an orexin neuropeptide was given to rodents to counteract the disruption. (ohsu.edu)
  • Intriguingly, loss of orexin prevents thermogenic energy expenditure while inducing obesity in the face of hypophagia. (lesswrong.com)
  • Thus, orexin is a unique neuropeptide that promotes both feeding and energy expenditure, conferring resistance to weight gain. (lesswrong.com)
  • Reports suggest that orexins may be the key brain components to mediate the mechanism of obesity resistance. (researchgate.net)
  • Here, we review a fat-burning mechanism that is turned on by the brain hormone orexin during high-caloric food consumption. (lesswrong.com)
  • Higher affinity and faster on/off receptor kinetics of DAYVIGO to orexin receptor 2, which also suppresses non-REM sleep, indicates its potential to facilitate non-sedative onset and maintenance of sleep. (eisai.com)
  • However, further research is required in this direction to elucidate the mechanisms by which orexins play a role in different testicular functions and effect of orexins on semen quality. (researchgate.net)
  • A Role for Orexin in Cytotoxic Chemotherapy-Induced Fatigue" was funded by grants from the National Institutes of Health (F31NR01329901,NINR 738 R01NR012479 and NIH R01 DK70333). (ohsu.edu)
  • Prior to this study, the Marks' laboratory conducted research demonstrating that fatigue following infection is associated with suppressed orexin-neuron function. (ohsu.edu)
  • Since chemotherapy was found to disrupt orexin neuron function, further investigation of orexin replacement for chemotherapy-induced fatigue is warranted based on the animal study results. (ohsu.edu)
  • Also in the RMS, higher levels of newly built cells in the orexin/ataxin group were found, but these differences were not significant. (uni-marburg.de)
  • Leucokinin neuropeptide (LK) and its receptor ( LK-R ) were found to be required for normal behavioral rhythms. (sdbonline.org)
  • These results show that orexin transmission at the orexin 1 receptor, but not the orexin 2 receptor, is necessary for the reinstatement of cocaine-seeking elicited by drug-paired cues and that orexin signaling is not critical for cocaine reinforcement or cocaine-stimulus conditioning. (tamu.edu)
  • For the evaluation of the stem cell proliferation in SVZ and SGZ and migration in the RMS, orexin/ataxin-3 mice (n = 8) and wild type (WT) mice (n = 8) received a single intraperitoneal injection of 100 mg BrdU (bromodeoxyuridine)/kg body weight 2 hour prior to sacrifice. (uni-marburg.de)
  • For the analysis of differentiation and survival of newly built cells, BrdU was administered intraperitoneally on 5 consecutive days once per day to orexin/ataxin-3 mice (n = 8) and WT mice (n = 8) and they were sacrificed 30 days after the last injection. (uni-marburg.de)
  • A tendency for higher survival rates could be shown for the HC of the orexin/ataxin-3 mice (not significant). (uni-marburg.de)