Regulation orexin. Medical search. Frequent questions

Orexin receptor type 2 (Ox2R or OX2), also known as hypocretin receptor type 2 (HcrtR2), is a protein that in humans is encoded by the HCRTR2 gene. (wikipedia.org)
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)
Hypothalamic orexin/hypocretin (Orx/Hcrt) peptides participate in the regulation of a wide range of physiological processes and are recruited by drugs of abuse. (healthyguide.info)
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)
Hypocretin is an alternative name in the literature for orexin, hypocretin-1 for orexin A, and hypocretin-1 for orexin B. (lesswrong.com)
We found that 75 mg/kg modafinil increased Fos immunoreactivity in the tuberomammillary nucleus (TMN) and in orexin (hypocretin) neurons of the perifornical area, two cell groups implicated in the regulation of wakefulness. (jneurosci.org)
In 2000, UCLA sleep researchers discovered that human narcolepsy - a condition where people are overwhelmed with daytime drowsiness and sudden attacks of sleep - was caused by a loss of roughly 90% of the 80,000 brain cells containing hypocretin (also called orexin), a chemical messenger important in the regulation of sleep and wakefulness. (uclahealth.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)
We are particularly interested in the hypocretin/orexin neurons, their signaling, and their involvement in the sleep disorder narcolepsy and in sleep-wake regulation during sickness in general. (ku.dk)
Hypocretin (also known as orexin) is a neurotransmitter involved in the regulation of the sleep/wake cycle as well as other bodily functions (e.g. blood pressure and metabolism). (narcolepsynetwork.org)
The histaminergic and hypocretin/orexin (hcrt) neurotransmitter systems play crucial roles in alertness/wakefulness in rodents. (elsevierpure.com)

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)
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)
These results suggest a functional connection between the two populations of hypothalamic neurons and that they may cooperate in the regulation of rapid-eye-movement sleep and feeding. (jneurosci.org)
Orexin neuropeptides (also known as hypocretins) are produced by a small group of neurons in the lateral hypothalamic and perifornical areas, a region classically implicated in the control of mammalian feeding behavior. (elsevierpure.com)
Orexin neurons project throughout the central nervous system (CNS) to nuclei known to be important in the control of feeding, sleep-wakefulness, neuroendocrine homeostasis, and autonomic regulation. (elsevierpure.com)
C-fos expression in orexin neurons, an indicator of neuronal activation, is positively correlated with wakefulness and negatively correlated with rapid eye movement (REM) and non-REM sleep states. (elsevierpure.com)
Orexins (also called hypocretins), which are neuropeptides exclusively expressed by a population of neurons specifically localized in the lateral hypothalamic area, are critically implicated in the regulation of sleep/wake states. (elsevierpure.com)
These neurons project to other hypothalamic nuclei and to the nucleus of the solitary tract in the brain stem to control multiple aspects of the homeostatic regulation of energy balance. (nature.com)
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)
These observations suggest that modafinil may promote waking via activation of TMN and orexin neurons, two regions implicated in the promotion of normal wakefulness. (jneurosci.org)
Where invertebrate 5-HT neurons promote an appetitive state, this role is supplanted in the vertebrates by a peptidergic network centered around orexins/hypocretins, to which the role of 5-HT in arousal is subordinate. (erowid.org)
Minireview: Regulation of Prohormone Convertases in Hypothalamic Neurons: Implications for ProThyrotropin-Releasing Hormone and Proopiomelanocortin Eduardo A. Nillni Division of Endocrinology, Department of Medicine, Brown Medical School/Rhode Island Hospital, and Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, Rhode Island 02903 Recent evidence demonstrated that posttranslational processing of neuropeptides is critical in the pathogenesis of obesity. (moam.info)
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)
Cannabinoid receptor (CBR) expression in this area is involved in modulating the function of orexin neurons. (bvsalud.org)
In this study, we investigated the effects of endocannabinoid anandamide (AEA) administration on improving food intake and appetite by modulating the activity of orexin neurons and CB1R expression after chronic sleep deprivation. (bvsalud.org)
Weight gain, food intake, the electrical power of orexin neurons, CB1R mRNA expression in hypothalamus, CB1R protein expression in the LH, TNF-α, IL-6, IL-4 levels and antioxidant activity in hypothalamus were measured after SD induction. (bvsalud.org)
The orexins are produced in neurons of the lateral hypothalamic area and implicated in the regulation of both feeding and reproductive function. (elsevierpure.com)
Using double- and triple-label immunofluorescence coupled with confocal microscopy, we found that 75-85% of GnRH neurons were contacted by orexin fibers, and triple labeling with synaptophysin provided additional confirmation of close contacts. (elsevierpure.com)
Furthermore, about 85% of GnRH neurons were colocalized with the orexin receptor 1 (OX-R1), and the OX-R1-expressing GnRH neurons were contacted by orexin terminals, providing the basis for a functional neuroanatomical pathway. (elsevierpure.com)
An additional study investigated the coexpression of neuropeptide Y Y4-like receptors and orexin fibers in relation to GnRH neurons. (elsevierpure.com)
The present study found that, although Y4-positive orexin fibers are in present in the area of GnRH neurons, they never come in close contact with GnRH neurons. (elsevierpure.com)
Together, these data suggest that Y4 receptor modulation of LH release is likely to be indirect through orexin cell bodies and that orexin modulates GnRH neurons directly via OX-R1. (elsevierpure.com)

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)
Orexin-A and orexin-B are neuropeptides originally identified as endogenous ligands for two orphan G-protein-coupled receptors. (elsevierpure.com)
Contextual generalization of social stress learning is modulated by orexin receptors in basolateral amygdala, 1-12. (usd.edu)
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)
Several AD mouse models revealed reduced orexin and its receptors, which leads to sleep disturbances and behavioral issues. (news-medical.net)
The current study was carried out to investigate the mRNA expression of the prepro-orexin gene (PPO) and orexin receptors (OX1R and OX2R) in ovarian follicles during different stages of their development in the ovary of water buffalo (Bubalus bubalis) and to determine the role of orexin on oestradiol production. (bvsalud.org)
Orexin-A and orexin receptors were localized in the cytoplasm of GC and TI, and intensity was higher in F3 and F4 follicles. (bvsalud.org)
G-protein coupled receptors for APELIN that function in a broad range of physiologic processes including blood pressure regulation and heart contractility. (bvsalud.org)

Orexins (or hypocretins) are hypothalamic neuropeptides with a multitude of physiological functions. (researchgate.net)
OX2 binds both orexin A and orexin B neuropeptides. (wikipedia.org)
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)

precursor, prepro-orexin (PPO). (researchgate.net)
We report here the sleep/wakefulness abnormalities in transgenic mice that exhibit widespread overexpression of a rat prepro-orexin transgene driven by a β-actin/ cytomegalovirus hybrid promoter (CAG/orexin transgenic mice). (elsevierpure.com)
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)

These findings suggest that the orexin neuropeptide system plays a significant role in feeding and sleep-wakefulness regulation, possibly by coordinating the complex behavioral and physiologic responses of these complementary homeostatic functions. (elsevierpure.com)
Thus, orexin is a unique neuropeptide that promotes both feeding and energy expenditure, conferring resistance to weight gain. (lesswrong.com)
The N-terminal α-helixes serve a critical roll in Orexin-A-mediated neuropeptide activation. (proteopedia.org)
Orexins A and B (ORA and ORB) are neuropeptide hormones found throughout the central nervous system and periphery. (warwick.ac.uk)
it is a neuropeptide with pleiotropic functions, including regulation of reproduction. (bvsalud.org)

These cells normally produce chemicals called hypocretins (also known as orexins), which have many important functions in the body. (medlineplus.gov)

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)

Daridorexant is a dual orexin receptor antagonist for the treatment of insomnia. (springer.com)

Intracerebroventricular administration of orexins has been shown to significantly increase food consumption, wakefulness, and locomotor activity in rodent models. (elsevierpure.com)
Targeted disruption of the orexin gene in mice produces a syndrome remarkably similar to human and canine narcolepsy, a sleep disorder characterized by excessive daytime sleepiness, cataplexy, and other pathological manifestations of the intrusion of REM sleep-related features into wakefulness. (elsevierpure.com)
Orexin deficiency results in narcoleptic phenotype in rodents, dogs, and humans, suggesting that orexins are important for maintaining consolidated wakefulness states. (elsevierpure.com)
Narcolepsy causes a lack of regulation of the sleep/wake cycle, and, thus, narcolepsy frequently causes both interruptions of a person's wakefulness and a person's REM sleep. (proteopedia.org)
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)

whereas a disrupted orexin system leads to narcolepsy. (jneurosci.org)
However, the physiological effect of constitutive increased orexinergic transmission tone, which might be important for understanding the effects of orexin agonists that are promising candidates for therapeutic agents of narcolepsy, has not been fully characterized. (elsevierpure.com)
Since OX1R and OX2R play important rolls in sleep regulation, sleep disorders, such as narcolepsy, can been caused by mutations of these regulators. (proteopedia.org)
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)

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)
Functioning as brain region for the regulation of energy homeostasis, the hypothalamus integrates different hormonal and neuronal signals controlling appetite and body weight. (frontiersin.org)
Sleep deprivation alters orexinergic neuronal activity in the lateral hypothalamus (LH), which is the main regulator of sleep-wake, arousal, appetite, and energy regulation processes. (bvsalud.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 is a neurotransmitter expressed in the hippocampus that controls sleep, motivated behavior, and excitability. (news-medical.net)

An innovative approach has been suggested based on the presence of orexin receptor (OX1R) in the inflamed human epithelium of UC patients. (bvsalud.org)

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)

and the orexin peptides have been implicated in physiological roles similar to those of HA. (jneurosci.org)
Our Peptides Involved in Appetite Modulation review gives an overview of the peptides implicated in appetite regulation and energy homeostasis. (tocris.com)
Leptin or other physiological changes affects the biosynthesis and processing of many peptides hormones as well as the regulation of the family of prohormone convertases responsible for the maturation of these hormones. (moam.info)

Consequently narcoleptic patients have very low cerebrospinal fluid levels of orexin. (uni-marburg.de)
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)

orexin mRNA expression is upregulated by fasting and insulin-induced hypoglycemia. (elsevierpure.com)
hdc mRNA injection alone led to an up-regulation of hcrt neuron numbers. (elsevierpure.com)

Furthermore, orexin knockout mice are hypophagic compared with weight and age-matched littermates, suggesting a role in modulating energy metabolism. (elsevierpure.com)
CAG/orexin mice exhibit sleep abnormalities with fragmentation of non-rapid eye movement (REM) sleep episode and a reduction in REM sleep. (elsevierpure.com)
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)
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)
A tendency for higher survival rates could be shown for the HC of the orexin/ataxin-3 mice (not significant). (uni-marburg.de)

Intriguingly, loss of orexin prevents thermogenic energy expenditure while inducing obesity in the face of hypophagia. (lesswrong.com)
Within this context, leptin provides the adipocyte-derived hormonal signaling allowing the bidirectional communication between adipose tissue and hypothalamic regulation of food intake and energy expenditure ( Zhou and Rui, 2013 ). (frontiersin.org)

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)
Nevertheless, the study performed by Merroun and colleagues [33] suggested the lateral hypothalamus-derived orexin A as a mediator of the anorexigenic effects induced by CB1 antagonist AM251 as well [33]. (researchgate.net)

Marked contrast, however, exists for roles of 5-HT in regulation of appetite. (erowid.org)
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)

SB 334867 is a selective non-peptide orexin OX 1 receptor antagonist. (tocris.com)

There is evidence that Y4 receptor stimulation results in LH release, and studies from our laboratory show Y4-like immunoreactivity in the majority of orexin cell bodies in the lateral hypothalamic area and some orexin fibers scattered throughout the hypothalamus. (elsevierpure.com)

Substantial evidence indicates that the brain, particularly the hypothalamus, is primarily responsible for the regulation of energy homeostasis. (nature.com)
Role of orexin in the regulation of glucose homeostasis. (bvsalud.org)

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)

Reports suggest that orexins may be the key brain components to mediate the mechanism of obesity resistance. (researchgate.net)
Accumulated evidence from genetic animal models suggests that the brain, particularly the hypothalamus, has a key role in the homeostatic regulation of energy and glucose metabolism. (nature.com)
Here we comprehensively review the above topics, discussing the main findings related to the role of the brain in the homeostatic regulation of energy and glucose metabolism. (nature.com)
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)
Here, we review a fat-burning mechanism that is turned on by the brain hormone orexin during high-caloric food consumption. (lesswrong.com)

It is suggested that the defect in orexins synthesis could be responsible for the disturbances in GH synthesis and consequently aggravate metabolic disturbances. (endocrine-abstracts.org)

a hormone that stimulates the appetite and is thought to be important for sleep regulation. (absp.org.uk)
They are required for a host of physiological processes including mitogen-activated protein kinase (MAPK) regulation, steroidogenesis, appetite control and energy regulation. (warwick.ac.uk)

Evidence thus implicates participation of orexins in steroidogenesis, spermatogenesis, transportation and maturation of sperm as well as in the control of penile function. (researchgate.net)

They occur in two known forms, namely, orexin A and orexin B with a common precursor, preproorexin. (researchgate.net)

The role of leptin and orexins in the dysfunction of hypothalamo-pituitary-gonadal regulation and in the mechanism of hyperactivity in patients with anorexia nervosa. (nel.edu)
Regulation of energy balance by leptin involves regulation of several proneuropeptides such as proTRH and proopiomelanocortin. (moam.info)

Orexins stimulate LH secretion in steroid-primed ovariectomized female rats and suppress LH secretion in nonprimed ovariectomized rats. (elsevierpure.com)

It has been reported that orexins play an important role in the regulation of GH secretion. (endocrine-abstracts.org)
The aim of the present study was to characterize the neuroanatomical pathway by which orexin might modulate LH secretion in the rat. (elsevierpure.com)

Histamine has also been shown to play a role in the regulation of sleep and feeding. (jneurosci.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 inhibitors (eg, lemborexant, suvorexant) are options for patients with difficulties of sleep onset and/or sleep maintenance. (medscape.com)

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)

Anatomy12

Organisms3

Diseases4

Chemicals and Drugs21

Analytical, Diagnostic and Therapeutic Techniques and Equipment6

Psychiatry and Psychology15

Phenomena and Processes12

Disciplines and Occupations1

Hypocretin12

Neurons32

Receptors14

Neuropeptides3

Prepro-orexin7

Neuropeptide5

Hypocretins1

Antagonists1

Dual orexin receptor antagonist1

Wakefulness5

Narcolepsy4

Neuronal5

OX2R2

Neurotransmitter1

OX1R1

Human orexin1

Peptides3

Narcoleptic2

MRNA2

Mice6

Energy expenditure2

Lateral hypothalamus3

Roles2

Selective1

Fibers1

Homeostasis2

Subtype1

Brain5

Synthesis1

Appetite2

Steroidogenesis1

Precursor1

Leptin2

Rats1

Secretion2

Role in the regulation1

Hypothalamus region1

Inhibitors1

Reproductive1