References Bqm
1. L. Lin, M. Hungs, and E. Mignot, Narcolepsy and the HLA region, J. Neuroimmunol. 117,9-20 2001 . 2. L. Lin, J. Faraco, R. Li, H. Kadotani, W. Rogers, X. Lin, X. Qiu, P. J. de Jong, S. Nishino, and E. Mignot, The sleep disorder canine narcolepsy is caused by a mutation in the hypocretin orexin receptor 2 gene, Cell 98,365-376 1999 . 3. R. M. Chemelli, J. T. Willie, C. M. Sinton, J. K. Elmquist, T. Scammell, C. Lee, J. A. Richardson, S. C. Williams, Y. Xiong, Y. Kisanuki, T. E. Fitch, M....
Rodent Models Of Pathophysiology Of Human Narcolepsy
Electrophysiological abnormalities in orexin-' are strikingly similar to human narcolepsy. However, unlike orexin-' mice as well as OX2R-dificient narcoleptic dogs, familial transmission of human narcolepsy is rare even in these rare cases penetrance is far less than 100 . No mutation has been found either in the prepro-orexin or orexin receptor genes of human narcolepsy-cataplexy patients except an unusually severe, early onset case, which is associated with mutation in the prepro-orexin gene...
New Lh Peptides
Recent identification of two LH-specific peptides has revitalized interest in the LH, by allowing for direct studies of specific gene function. The ORX HCRT and melanin- concentrating hormone MCH neuropeptides are localized to non-overlapping sets of neurons within the LH and have powerful effects on behavior. The ORX HCRT gene product was independently isolated by two research groups and was found to exist in two forms which are the result of differential post-translational processing.1516...
Hypocretin Excites Midline Intralaminar Thalamic Neurons
Hypocretin has been shown selectively to depolarize midline-intralaminar thalamic neurons and not sensory thalamic neurons.16 Such specificity is congruent with previous observations that hypocretin fibers avoid specific sensory thalamic nuclei, terminating predominantly in midline-intralaminar nuclei such as rhomboid and central medial.12 Midline-intralaminar nuclei show prominent expression of the hypocretin receptor 2,1718 which is very sensitive to both hypocretin peptides. Bayer and...
Antipsychotic Drugs And Orexin Neurons
The ability of DA agonists to activate orexin cells, particularly those in the medial LH PFA, suggests that drugs that block DA receptors may also modulate the activity of orexin neurons. We were particularly interested in antipsychotic drugs APDs because treatment of schizophrenics with many of these drugs causes marked weight gain,19 leading to problems with patient compliance and inhibiting psychosocial integration, and because orexin potently produces feeding.20-22 All APDs have some D2...
The Suprachiasmatic Nucleus
The suprachiasmatic nucleus SCh is the major biological clock of the brain and provides an entrance for visual afferent signals to the circadian circuitry of the brain.136, 137 see ref 138 A direct projection from the SCh to both the Hcrt and MCH cells has been described in both rat and human brain 67 see also ref 139. These projections derive from the shell predominantly containing the neuropeptide, arginine-vasopressin as well as the core predominantly containing the neuropeptide, vasoactive...
Parallel Pathways from the Arcuate Nucleus to the LHA
By the late 1990's, it was thus evident that the arcuate nucleus plays a central role in the initiation of the body's response to starvation. Still, it was not known which brain regions lie downstream in the circuitry. Only the dorsomedial and paraventricular hypothalamic nucleus had been anatomically identified as direct targets of the arcuate nucleus NPY neurons.114 Injection of NPY into these structures had also been reported to elicit feeding responses. However, the most potent stimulation...
Dopaminergic Regulation Of Orexin Neurons
In view of the relatively dense dopaminergic innervation of the LH PFA, we undertook an examination of the ability of indirect and direct DA agonists on the activity of orexin neurons, as reflected by induction of Fos, the protein product of the early- immediate gene c-fos. Because orexin neurons are a small population of LH PFA cells that are scattered across the dorsal hypothalamus, reporters such as Fos are particularly useful in indicating the impact of a pharmacological treatment12 on...
References Qep
1. C. Westphal, Eigenth mliche mit Einschlafen verbundene Anf lle, Archiv Psychiat.Nervenkr. 7, 631-635 2. J. B. Gelineau, De la narcolepsie, Gaz.H p. Paris 53, 626-628 1880 . 3. R. Broughton, V. Valley, M. Aguirre, J. Roberts, W. Suwalski, and W. Dunham, Excessive daytime sleepiness and the pathophysiology of narcolepsy- cataplexy a laboratory perspective, Sleep 9, 205-215 1986 . 4. S. Nishino, J. Riehl, J. Hong, M. Kwan, M. S. Reid, and E. Mignot, Is narcolepsy a REM sleep disorder Analysis...
Dementia
Alzheimer disease is the most frequent cause of dementia with frequent sleep wake cycle disturbances and alterations of circadian rhythms. Patients affected with Alzheimer disease had normal levels of CSF hypocretin-1.7,14 In addition, no correlation between the CSF hypocretin levels and normal ageing has been reported. Dementia with Lewy bodies DLB is a rare cause of dementia associated with a progressive cognitive decline, fluctuations in cognition, recurrent visual hallucinations and...
Structures And Pharmacology Of Orexin Receptors
Initially, we used an orphan GPCR termed HFGAN72 which now named as orexin-1 receptor, OX1R or hcrtrl to identify orexins. Since we found that orexin B has significaltly lower affinity for the human OX1R , we sought other orexin receptors for which orexin B has high affinity. A BLAST search of the dbEST database with the OX1R amino acid sequence detected another orexin receptor, orexin-2 receptor OX2R, or hcrtr2.2 The actions of orexins are mediated by these two receptors.2 Among various...
Conclusion Nkp
In summary, deficient hypocretin-1 transmission is highly specific and sensitive for sporadic narcolepsy with typical excessive daytime somnolence, cataplexy and HLA DQB1 0602 allele. Hypocretin ligand deficiency appears not to be the major cause for other hypersomnias but a pathophysiological continuum between narcolepsy without cataplexy and idiopathic hypersomnia could be hypothesized. Undetectable CSF hcrt-1 levels are highly sensitive and specific for narcolepsy and are a useful diagnostic...
Arc
0.080 0.001 0.021 0.000 0.058 0.004 0.091 0.003 0.022 0.000 0.061 0.005 Table 1. Effects of a 4-hour high-fat diet compared to a low-fat diet. p lt 0.05 for comparisons between low-fat and high-fat diet scores. Peptide expression is calculated as a ratio to P-actin mRNA. Abbreviations TG, triglycerides NEFA, non-esterified fatty acids PVN, paraventricular nucleus PFH, perifornical lateral hypothalamus ARC, arcuate nucleus. Similar to the high-fat diet, injection of Intralipid, a fat emulsion...
Role Of Csf Hypocretin In The Diagnosis Of Narcolepsy
These new neurobiologic hypocretin deficiency and genetic HLA findings have lead to a redefinition of narcolepsy. Whereas the MSLT has been classically used to distinguish, for example, narcolepsy without cataplexy from idiopathic hypersomnia, the expanded disease continuum of the narcolepsy clinical borderland has made the diagnosis of narcolepsy more difficult. As such, the use of CSF Hcrt-1 levels as a biologically-based diagnostic test for narcolepsy has been particularly useful in...
Histaminergic System And Narcolepsy
After the discoveries of the involvement of the hypocretin system in narcolepsy, we focused on how these deficits in hypocretin neurotransmission induce narcolepsy. One of the keys to solving this question is revealing the functional differences between Hcrtr 1 and Hcrtr 2, since it is evident that Hcrtr 2-mediated function plays a critical role in generating narcoleptic symptoms in canine model.73 In situ hybridization experiments in rats demonstrated that Hcrtr 1 is enriched in the...
Ventrolateral Preoptic Area
The ventrolateral preoptic area VLPO provides inhibitory innervation of major monoaminergic arousal systems, via neurons containing GABA and the neuropeptide galanin.146 147 Several lines of evidence implicate the VLPO GABA galanin cells as sleep-promoting neurons 1 see ref 93. This region receives a small projection from both Hcrt and MCH neurons.148 While a reciprocal pathway has not been described, there is functional data suggesting that Hcrt neurons may be under control of the VLPO. When...
Cat
Figure 3. Sleep waking cycle discharge of monoaminergic cells. Monoaminergic cells behave similarly across normal sleep cycles, with all showing maximal discharge in active waking, decreased discharge in quiet waking, greatly reduced discharge in sow wave sleep SWS and minimal discharge in REM sleep. In cataplexy, noradrenergic locus coeruleus cells are off, whereas histaminergic cells are on and serotonergic dorsal raphe cells have an intermediate pattern From ref 7 . 4. ARE HYPOCRETINS...
Inhibitory Response To Norepinephrine And Serotonin
Hypocretin neurons project to the dorsal raphe and locus coeruleus3, two systems involved in aspects of arousal.21 In the locus coeruleus, hypocretin axons make direct synaptic contact with asymmetrical-type synapses.22 Hypocretin excites locus coeruleus neurons by several mechanisms, in large part by activation of the hypocretin receptor 1 Ox1R .31'22'32'33'34 Hypocretin increased action potentials and spike synchrony in the norepinephrine containing cells of the mouse locus coeruleus Figure...
Uc Davis Sleep Hypocretin
Human narcolepsy is a chronic sleep disorder that affects 1 2000 of the general population. One of the major research aims of the Stanford Sleep Research Center is to find the etiology of the disease and to develop better treatments for human narcolepsy. However, human narcolepsy is very complex and multifactorial, and is 1 genetically heterogeneous, 2 a polygenic trait and 3 environmentally influenced.1 The development of a simpler animal model of narcolepsy was thus the high priority in the...
Experimental
Our methods for preparation of brainslices, whole-cell recordings, immunocytochemistry43 and calcium imaging44,45 have been previously described in detail and are only briefly summarized here. Brain slices were prepared from 14-32 day old C57 Bl6 mice in ice-cold artificial cerebrospinal fluid ACSF which contained in mM 121 NaCl, 5 KCl, 1.2 NaH2PO4, 2.7 CaCl2, 1.2 MgSO4, 26 NaHCO3, 20 dextrose, 4.2 lactic acid and was oxygenated by bubbling with carbogen 95 O2 and 5 CO2 . Slices containing the...
Hippocampus And Cortex
Hypocretins and biogenic amines and their cognate receptors densely accumulate in infralimbic structures including the amygdala, hippocampus, and insular, cingulated, and prefrontal cortex. Apart from convergent, direct excitatory effects of hypocretins on nonspecific thalamic relay neuronsl35 and intracortically projecting layer 6b neurons 36 the orchestration of aminergic, glutamatergic, and GABAergic signals provides a powerful mechanism promoting cortical activation, plasticity, and...
References 1
1. H. Usui, J. Falk, A. Dopazo, L. de Lecea, M. G. Erlander and J. G. Sutcliffe, Isolation of clones of rat striatum-specific mRNAs by directional tag PCR subtraction, J. Neurosci. 14,4915-4926 1994 . 2. K. M. Gautvik, L. de Lecea, V. T. Gautvik, P. E. Danielson, P. Tranque, A. Dopazo, F. E. Bloom and J. G. Sutcliffe, Overview of the most prevalent hypothalamus-specific mRNAs, as identified by directional Tag PCR subtraction, Proc. Natl. Acad. Sci. USA 93, 8733-8738 1996 . 3. L. de Lecea, T. S....
References
1. J. G. Sutcliffe, pBR322 and the advent of rapid DNA sequencing, TIBS 20, 87-90 1995 . 2. T. M. Shinnick, R. A. Lerner and J.G. Sutcliffe, Nucleotide sequence of Moloney murine leukemia virus, 3. S. Nakanishi, A. Inoue, T. Kita, M. Nakamura, A. C. Chang, S. N. Cohen and S. Numa, Nucleotide sequence of cloned cDNA for bovine corticotropin-beta-lipotropin precursor, Nature 278, 423-427 1979 . 4. J. G. Sutcliffe, T. M. Shinnick, N. Green, F.-T. Liu, H. L. Niman and R. A. Lerner, Chemical...
Neurons123
123 2. HYPOCRETIN NEURONS SHOW SPONTANEOUS REGULAR ACTION 124 3. SYNAPTIC INPUT TO HYPOCRETIN NEURONS IS MEDIATED BY GLUTAMATE AND 4. INHIBITORY RESPONSE TO NOREPINEPHRINE AND SEROTONIN 126 5. HYPOCRETIN ACTIVATES HYPOCRETIN NEURONS BY AN INDIRECT EXCITATION OF GLUTAMATERGIC INTERNEURONS 128 6. GROUP 3 METABOTROPIC GLUTAMATE RECEPTORS INHIBIT HYPOCRETIN 128 7. GLUCAGON-LIKE PEPTIDE 1 EXCITES HYPOCRETIN NEURONS 132 8. METABOLIC SIGNALS MODULATE HYPOCRETIN NEURON 132 133 133 9. THE NE SYSTEM AS...
Dopamineregic Transmission and EEG Arousal
Narcoleptic Dobermans were also used for a series of pharmacological experiments to dissect modes of action of wake-promoting compounds. Amphetamine-like CNS stimulants currently used clinically for the management of sleepiness in narcolepsy enhance monoaminergic transmission presynaptically. Figure 4. Effects of various DA and NE uptake inhibitors and amphetamine-like stimulants on the EEG arousal of narcoleptic dogs and correlation between in vivo EEG arousal effects and in vitro DAT binding...
Genetic Aspects Of Narcolepsy
A genetic component to narcolepsy was suggested by Westphal's 1877 initial report, in which both the patient and his mother were afflicted with the condition. Recent studies have, though, indicated that narcolepsy-cataplexy is only rarely a familial disorder. Only 1 to 2 of first-degree narcolepsy relatives ever develop the disorder 29 it is interesting to note however, that this 1 to 2 increase in risk represents a 20 to 40-fold increased risk over the prevalence in the general population...
Symptoms Of Canine Narcolepsy
Affected dogs exhibit very pronounced attacks of cataplexy which are mainly triggered by positive emotional experiences , such as being fed a favorite food or engaging in play. Cataplectic attacks in dogs often begin as a buckling of both hind legs, and this is often accompanied by a drooping of the neck see Figure 1 . The dog may collapse to the floor and remain motionless for a few seconds or several minutes. In contrast to the some forms of epilepsy, excess salivation or incontinence are not...
Info Vif
Table 1 Rodent narcolepsy models produced by genetic engineering Table 1 Rodent narcolepsy models produced by genetic engineering T. Sakurai, Institute of Basic Medical Science, Departments of Pharmacology, University of Tsukuba, Ibaraki 305-8575, Japan T. Sakurai and M. Yanagisawa, ERATO Yanagisawa Orphan Receptor Project, Japan Science and Technology Corporation, Tokyo 135-0064, Japan M. Mieda, Department of Molecular Neuroscience, Medical Research Institute, Tokyo Medical and Dental...
Pain Disorders
The regulation of pain perception is another function in which the hypothalamus plays a part. The destruction of the posterior hypothalamus caused transient hyperalgesia in rats and the electrical stimulation of this structure can relieve pain. Functional abnormalities of the hypothalamus have been proposed in the initiation of central pain disorders such as in cluster headache and migraine. In addition, hypocretin neurons have mu-opioid receptors and respond to chronic morphine administration...
Afferent Connections Of Hcrt Neurons
The afferent innervation of Hcrt neurons is less well understood. Colocalization of Hcrt with receptors for the neurotransmitters GABA92 and NPY34 suggests that Hcrt neurons are innervated by GABAergic and NPYergic neurons. GABAergic innervation may arise locally from GABAergic neurons that are abundant in the hypothalamus.93 NPY, agouti-related peptide AgRP , and alpha-MSH are neurotransmitters found in the arcuate nucleus of the hypothalamus, an important regulator of food intake and body...
Fasting Small Bowel Motility
Few studies have examined the effects of peripheral hcrt orexin 1 on gastrointestinal function in vivo. In vitro, hcrt orexin 1 has been demonstrated to increase colonic motility in guinea pigs.10 In both rats and humans, fasting small bowel motility is characterized by the myoelectric motor complex MMC . The MMC is characterized by three phases in phase 1 there is motor quiescence, in phase 2 irregular spiking and in phase 3 a propagated motor pattern resulting in an activity front. In rats...
Hypocretin Deficiency In Human Narcolepsy
In 1999, it was discovered that a genetically induced deficiency of hypocretin neurotransmission in dogs and mice leads to a complex of symptoms remarkably similar to that seen in human narcolepsy.6'7 These findings focused attention on the role of hypocretin in the pathophysiology of human narcolepsy. A mutation screening of the hypocretin genes was performed in 74 patients, including patients with and without a family history of narcolepsy and patients with and without HLA DQB1 0602.8 Of...
Localization Of Hcrt Receptors
The distribution of Hcrt receptors is largely consistent with Hcrt axon innervation patterns Fig. 2 . However, a differential distribution of the two Hcrt receptors, HcrtR1 and HcrtR2, has been demonstrated in several brain regions in both in situ hybridization82-84 and immunohistochemical85,86 studies. In the cerebral cortex, hcrtrl mRNA is expressed primarily in layers II, III and V, whereas hcrtr2 mRNA is found at higher density in layers II and VI and more diffusely in other layers Fig. 2 ....
References Ysm
1. C. Peyron, D. K. Tighe, A. N. van den Pol, L. de Lecea, H. C. Heller, J. G, Sutcliffe and T. S. Kilduff, Neurons containing hypocretin orexin project to multiple neuronal systems, J. Neurosci. 18 23 , 999610015 1998 . 2. J. N. Marcus, C. J. Aschkenasi, C. E. Lee, R. M. Chemelli, C. B. Saper, M. Yanagisawa and J. K. Elmquist, Differential expression of orexin receptors 1 and 2 in the rat brain, J. Comp. Neurol. 435, 6-25 2001 . 3. G. J. Hervieu, J. E. Cluderay, D. C. Harrison, J. C. Roberts...
Hypocretin And The Central Arm Of The Hpa Axis
The first hints that endogenous hypocretins orexins might be involved in the central component of the HPA axis came from one of the initial descriptions of the behavioral effects of the peptides.14 In addition to stimulating increased locomotor activity and grooming behaviors, responses similar to those observed following central administration of CRH, intracerebroventricular i.c.v. injection of orexin A resulted in increased corticosterone levels in conscious male rats. Growth hormone levels...
Inputs From The Basal Ganglia
Kelley and colleagues have studied a pathway from the nucleus accumbens to the LHA. Such a connection was early demonstrated with tracing techniques.73,74 Subsequent studies revealed that GABAergic spiny projection neurons in the shell region provide a diffuse innervation of the LHA in its entire rostrocaudal length.181 In contrast, the accumbal core region supplies terminals only in the LHA region bordering on the entopeduncular nucleus .182 When glutamatergic excitation is blocked in the...
Nonrem Sleeprelated Symptoms
Increased daytime sleepiness is well described in human patients.7'13 Human patients often complain of involuntary or irresistible urge to sleep, which can occur while talking, standing, walking, eating, or driving. In addition to REM sleep-related abnormalities, another prominent feature of sleep wake patterns in orexin-' mice or orexin ataxin-3 mice was shortened durations of both wakefulness and non-REM sleep in the dark phase, causing increased fragmentation of sleep wake cycle Fig. 3 ....
Hypocretin Deficiency In Narcolepsy
Nishino et al.5S found lumbar CSF Hcrt-1 levels below the detection limit 40 pg mL in narcoleptics, while control subjects had an average of 280 pg mL. This study provided the first clear link between hypocretin dysfunction and human narcolepsy. These findings have been extended and replicated by other groups59 see below . It has thus far not been possible to measure Hcrt-2 in the CSF, as Hcrt-2 is likely degraded rapidly or is unstable in CSF. Further pathologic evidence of selective...
Light Microscopy
Tamas L. Horvath, Department of Obstetrics, Gynecology amp Reproductive Sciences and Department of Neurobiology, Yale University School of Medicine, New Haven CT 06520, USA The region in which Hcrt neurons are located is frequently referred to as the lateral hypothalamus LH . However, Hcrt cells are not limited to the LH proper but rather, they occupy a space that includes parts of the LH and perifornical area with some cells present in the vicinity of the dorsomedial, paraventricular and...
Psychiatric Disorders
Many years of research have demonstrated the ability of the hypothalamus to control the homeostatic state and physiology in animals. Specific lesions experiments have characterized sub-nuclei of the hypothalamus that are important in sleep, feeding, autonomic control, sex drive and motivational behavior. The hypocretin neurons that are located in the dorso-lateral hypothalamus provide a dense innervation to the other nuclei within the hypothalamus as well as the monoaminergic systems, in...
Monoaminergic and Cholinergic Interactions and Cataplexy
The importance of increased cholinergic activity in triggering REM sleep or REM sleep atonia is well established see ref. 32 . Similarly, activation of the cholinergic systems using the acetylcholinesterase inhibitor physostigmine also greatly exacerbates cataplexy 33. This cholinergic effect is mediated via muscarinic receptors since muscarinic stimulation aggravates cataplexy, while its blockade suppresses it, and nicotinic stimulation or blockade has no effect.33 Monoaminergic transmission...
The Anatomical Framework
The paraventricular nucleus of the hypothalamus PVN is a paired cluster of neurons adjacent to the walls of the dorsal aspect of the third cerbroventricle. It is situated medial and adjacent to the hypocretin orexin-producing cells of the lateral hypothalamus perifornical area, some of which directly innervate the PVN.1 Both hypocretin receptors hcrtr1 and hcrtr2 are present in the PVN,2'3 with the hcrtr2 most abundant.4 The PVN is the central commander of the HPA axis and is the site of...
Introduction Fvj
As evidenced by the narcoleptic syndrome that occurs in mice following knock out of the gene for the peptide hypocretin orexin Hcrt Orx ,1 in dogs following knock out of the gene for Hcrt Orx receptors2 and in humans in association with the loss of Hcrt Orx peptide and neurons,3' 4 Hcrt Orx appears to be essential for the maintenance of waking. This role may be fulfilled through the widespread projections and influence of the Hcrt Orx neurons on multiple systems including the...
Distribution Of Hcrt Efferent Axons
The morphology of Hcrt-immunoreactive axons is heterogeneous and varies from thick, densely-varicose to fine, lightly-varicose.10 Hcrt-immunoreactive axons are found throughout the brain, with the highest density of terminal fields seen in the hypothalamus Fig. 1 .5,7,8 Figure 1. Schematic diagram of the pathways taken by Hcrt orexin axons, which widely innervate the rat brain through both ascending and descending projections.6 Copyright 1998 by the Society for Neuroscience. Figure 1. Schematic...
The Aminergic Systems
The relatively small number of aminergic neurons located in the locus coeruleus noradrenaline , dorsal raphe serotonin , ventral tegmental area substantia nigra dopamine , lateral dorsal tegmentum basal forebrain acetylcholine , and tuberomamillary nucleus histamine project with multifold arborisations to most regions of the central nervous system, partially overlapping with the projections of hypocretin neurons.32 Apart from some distinctions they display comparable morphological features,...
Hcr1
Figure 3. Hcrt-evoked depolarization demonstrates voltage dependence. a1,2 Two depolarizing responses to a puff application of Hcrt-2 as in Fig. 1 . Both responses were recorded in the same cell, either at resting membrane potential a1 , or 10 min later when the cell was hyperpolarized to -85mV a2 . Note a smaller depolarization in the latter. b Three puff applications of Hcrt-2 30 s application to the same cell, at 10 min intervals and different membrane potentials as indicated. The first...
References Jkf
1. L. de Lecea, T. S. Kilduff, C. Peyron, X.-B. Gao, P. E. Foye, P. E. Danielson, C. Fukuhara, E. L. F. Battenberg, V. T. Gautvik, F. S. Bartlett II, W. N. Frankel, A. N. van den Pol, F. E. Bloom, K. M. Gautvik and J. G. Sutcliffe, The hypocretins hypothalamus-specific peptides with neuroexcitatory activity, Proc Natl Acad Sci U S A. 95, 322-7. 1998 . 2. T. Sakurai, A. Amemiya, M. Ishii, I. Matsuzaki, R. M. Chemelli, H. Tanaka, S. C. Williams, J. A. Richardson, G. P. Kozlowski, S. Wilson, J. R....
Hypocretin Actions In The Adrenal Gland
Although it was originally thought that the sole locus of hypocretin production was in hypothalamus, some of the peptide may be produced in testis.32'38 Whether the hypocretin apparently produced in testis, or peptide produced in brain, gains access to the general circulation in sufficient amounts to act as a true hormone is unknown. However, hypocretin receptors are present in a variety of peripheral tissues, including the adrenal gland.33'42-45 In vitro studies have demonstrated significant...
Other Neurological Disorders
Low hypocretin levels are also observed in a large range of other neurological conditions. In these disorders the alteration of the hcrt level may reflect focal lesions in the hypothalamus or transient or chronic dysfunction of the hypothalamus. 4.1. Kleine-Levin Syndrome KLS KLS is a rare cause of hypersomnia characterized by a recurrent alteration of sleep-wake regulation and frequent abnormal feeding and sexual behaviors. Recent association reported with HLA DQB1 0201 together with the young...
Signal Transduction Systems Of Orexin Receptors
Both OX1R and OX2R are G-protein coupled receptors, which transmit information into cells by activating heterotrimeric G proteins. Activation of the signaling pathways associated with distinct G-proteins may contribute to the diverse physiological roles of orexin in particular neurons. Although many G-protein-coupled neurotransmitter receptors are potentially capable of modulating both voltage-dependent calcium channels and G-protein-gated inwardly rectifier potassium channels GIRKs , there...