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Hypocretin

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https://www.readbyqxmd.com/read/28209438/excessive-daytime-sleepiness-in-a-patient-with-coexisting-myotonic-dystrophy-type-1-myasthenia-gravis-and-graves-disease
#1
Katarzyna Kapica-Topczewska, Robert Pogorzelski, Joanna Tarasiuk, Wiesław Drozdowski, Piotr Lewczuk, Alina Kułakowska
A 41-year-old female with history of Graves' disease, bilateral cataract, paroxysmal atrial fibrillation was admitted because of muscle weakness, daytime sleepiness, fatigability, drowsiness, bilateral eyelid ptosis, descending of head and lower jaw. On neurological examination the patient was presented with muscle weakness, muscle atrophy (in face and sternocleidomastoid muscles), features of myotonia and apocamnosis (orbicular muscles). Electromyography revealed myopathic changes, myotonic and pseudomyotonic discharges, positive repetitive nerve stimulation test in proximal muscles...
February 3, 2017: Neurologia i Neurochirurgia Polska
https://www.readbyqxmd.com/read/28179647/narcolepsy
#2
REVIEW
Birgitte R Kornum, Stine Knudsen, Hanna M Ollila, Fabio Pizza, Poul J Jennum, Yves Dauvilliers, Sebastiaan Overeem
Narcolepsy is a chronic sleep disorder that has a typical onset in adolescence and is characterized by excessive daytime sleepiness, which can have severe consequences for the patient. Problems faced by patients with narcolepsy include social stigma associated with this disease, difficulties in obtaining an education and keeping a job, a reduced quality of life and socioeconomic consequences. Two subtypes of narcolepsy have been described (narcolepsy type 1 and narcolepsy type 2), both of which have similar clinical profiles, except for the presence of cataplexy, which occurs only in patients with narcolepsy type 1...
February 9, 2017: Nature Reviews. Disease Primers
https://www.readbyqxmd.com/read/28145492/hypocretin-orexin-peptides-excite-rat-neuroendocrine-dopamine-neurons-through-orexin-2-receptor-mediated-activation-of-a-mixed-cation-current
#3
David J Lyons, Arash Hellysaz, Rachida Ammari, Christian Broberger
Hypocretin/Orexin (H/O) neurons of the lateral hypothalamus are compelling modulator candidates for the chronobiology of neuroendocrine output and, as a consequence, hormone release from the anterior pituitary. Here we investigate the effects of H/O peptides upon tuberoinfundibular dopamine (TIDA) neurons - cells which control, via inhibition, the pituitary secretion of prolactin. In whole cell recordings performed in male rat hypothalamic slices, application of H/O-A, as well as H/O-B, excited oscillating TIDA neurons, inducing a reversible depolarising switch from phasic to tonic discharge...
February 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28108192/epidemiology-and-pathophysiology-of-childhood-narcolepsy
#4
REVIEW
Thomas J Dye, Neepa Gurbani, Narong Simakajornboon
It is now recognized that there are two types of narcolepsy. Narcolepsy type I or Narcolepsy with cataplexy is caused by the loss of hypocretin or orexin neurons. Narcolepsy type II or narcolepsy without cataplexy has normal hypocretin and the etiology is unknown. Hypocretin is a neuropeptide produced by neurons in the lateral hypothalamus. Both genetic and environmental factors play a crucial role in the pathogenesis of narcolepsy. Most patients with narcolepsy type I and half of patients with narcolepsy type II carry HLA-DQB1*0602...
December 21, 2016: Paediatric Respiratory Reviews
https://www.readbyqxmd.com/read/28107375/narcolepsy-type-1-is-associated-with-a-systemic-increase-and-activation-of-regulatory-t-cells-and-with-a-systemic-activation-of-global-t-cells
#5
Michel Lecendreux, Guillaume Churlaud, Fabien Pitoiset, Armelle Regnault, Tu Anh Tran, Roland Liblau, David Klatzmann, Michelle Rosenzwajg
Narcolepsy is a rare neurologic disorder characterized by excessive daytime sleepiness, cataplexy and disturbed nocturnal sleep patterns. Narcolepsy type 1 (NT1) has been shown to result from a selective loss of hypothalamic hypocretin-secreting neurons with patients typically showing low CSF-hypocretin levels (<110 pg/ml). This specific loss of hypocretin and the strong association with the HLA-DQB1*06:02 allele led to the hypothesis that NT1 could be an immune-mediated pathology. Moreover, susceptibility to NT1 has recently been associated with several pathogens, particularly with influenza A H1N1 virus either through infection or vaccination...
2017: PloS One
https://www.readbyqxmd.com/read/28100828/an-integrated-modelling-framework-for-neural-circuits-with-multiple-neuromodulators
#6
Alok Joshi, Vahab Youssofzadeh, Vinith Vemana, T M McGinnity, Girijesh Prasad, KongFatt Wong-Lin
Neuromodulators are endogenous neurochemicals that regulate biophysical and biochemical processes, which control brain function and behaviour, and are often the targets of neuropharmacological drugs. Neuromodulator effects are generally complex partly owing to the involvement of broad innervation, co-release of neuromodulators, complex intra- and extrasynaptic mechanism, existence of multiple receptor subtypes and high interconnectivity within the brain. In this work, we propose an efficient yet sufficiently realistic computational neural modelling framework to study some of these complex behaviours...
January 2017: Journal of the Royal Society, Interface
https://www.readbyqxmd.com/read/28095967/intravenous-immunoglobulin-therapy-in-pediatric-narcolepsy-a-nonrandomized-open-label-controlled-longitudinal-observational-study
#7
Michel Lecendreux, Johanna Berthier, Jennifer Corny, Olivier Bourdon, Claire Dossier, Christophe Delclaux
STUDY OBJECTIVES: Previous case reports of intravenous immunoglobulins (IVIg) in pediatric narcolepsy have shown contradictory results. METHODS: This was a nonrandomized, open-label, controlled, longitudinal observational study of IVIg use in pediatric narcolepsy with retrospective data collection from medical files obtained from a single pediatric national reference center for the treatment of narcolepsy in France. Of 56 consecutively referred patients with narcolepsy, 24 received IVIg (3 infusions administered at 1-mo intervals) in addition to standard care (psychostimulants and/or anticataplectic agents), and 32 continued on standard care alone (controls)...
January 11, 2017: Journal of Clinical Sleep Medicine: JCSM: Official Publication of the American Academy of Sleep Medicine
https://www.readbyqxmd.com/read/28093335/intracoerulear-microinjection-of-orexin-a-induces-morphine-withdrawal-like-signs-in-rats
#8
Masoumeh Ghaemi-Jandabi, Hossein Azizi, S Mohammad Ahmadi-Soleimani, Saeed Semnanian
Orexin (hypocretin) neuropeptides play a pivotal role in expression of opioid withdrawal signs. Hypothalamic orexinergic neurons provide dense afferents for the nucleus locus coeruleus (LC). Somatic signs of opioid withdrawal are associated with the enhanced activity of LC neurons. In addition, intra-LC administration of orexin-A leads to the hyperactivity of LC neurons. The present study was an attempt to investigate whether intra-LC microinjection of orexin-A induces morphine withdrawal-like signs in both morphine dependent and control rats...
January 16, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28090682/pituitary-macrotumor-causing-narcolepsy-cataplexy-in-a-dachshund
#9
S Schmid, A Hodshon, S Olin, I Pfeiffer, S Hecht
Familial narcolepsy secondary to breed-specific mutations in the hypocretin receptor 2 gene and sporadic narcolepsy associated with hypocretin ligand deficiencies occur in dogs. In this report, a pituitary mass is described as a unique cause of narcolepsy-cataplexy in a dog. A 6-year-old male neutered Dachshund had presented for acute onset of feeding-induced cataplexy and was found to have a pituitary macrotumor on magnetic resonance imaging (MRI). Cerebral spinal fluid hypocretin-1 levels were normal, indicating that tumor effect on the ventral lateral nucleus of the hypothalamus was not the cause of the dog's narcolepsy-cataplexy...
January 15, 2017: Journal of Veterinary Internal Medicine
https://www.readbyqxmd.com/read/28089263/adiponectin-orexin-a-and-orexin-b-concentrations-in-the-serum-and-uterine-luminal-fluid-during-early-pregnancy-of-pigs
#10
Nina Smolinska, Marta Kiezun, Kamil Dobrzyn, Karol Szeszko, Anna Maleszka, Tadeusz Kaminski
Adiponectin is the most abundant adipose-released protein that circulates in human plasma at high concentrations. The neuropeptides orexin A (OXA, hypocretin-1) and orexin B (OXB, hypocretin-2) are derived from a common precursor peptide, prepro-orexin and are produced mainly by neurons located in the lateral hypothalamus. It has been demonstrated that the peptides such as adiponectin and orexins have an important role in the regulation of energy metabolism and neuroendocrine functions. These hormones appear to be implicated in both normal and disturbed pregnancy...
January 9, 2017: Animal Reproduction Science
https://www.readbyqxmd.com/read/28087252/novel-method-for-evaluation-of-eye-movements-in-patients-with-narcolepsy
#11
Julie A E Christensen, Lykke Kempfner, Helle L Leonthin, Mathias Hvidtfelt, Miki Nikolic, Birgitte Rahbek Kornum, Poul Jennum
BACKGROUND: Narcolepsy causes abnormalities in the control of wake-sleep, non-rapid-eye-movement (non-REM) sleep and REM sleep, which includes specific eye movements (EMs). In this study, we aim to evaluate EM characteristics in narcolepsy as compared to controls using an automated detector. METHODS: We developed a data-driven method to detect EMs during sleep based on two EOG signals recorded as part of a polysomnography (PSG). The method was optimized using the manually scored hypnograms from 36 control subjects...
December 21, 2016: Sleep Medicine
https://www.readbyqxmd.com/read/28074859/identifying-a-gene-expression-signature-of-cluster-headache-in-blood
#12
Else Eising, Nadine Pelzer, Lisanne S Vijfhuizen, Boukje de Vries, Michel D Ferrari, Peter A C 't Hoen, Gisela M Terwindt, Arn M J M van den Maagdenberg
Cluster headache is a relatively rare headache disorder, typically characterized by multiple daily, short-lasting attacks of excruciating, unilateral (peri-)orbital or temporal pain associated with autonomic symptoms and restlessness. To better understand the pathophysiology of cluster headache, we used RNA sequencing to identify differentially expressed genes and pathways in whole blood of patients with episodic (n = 19) or chronic (n = 20) cluster headache in comparison with headache-free controls (n = 20)...
January 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28061506/role-of-rem-sleep-melanin-concentrating-hormone-and-orexin-hypocretin-systems-in-the-sleep-deprivation-pre-ischemia
#13
Marta Pace, Antoine Adamantidis, Laura Facchin, Claudio Bassetti
STUDY OBJECTIVES: Sleep reduction after stroke is linked to poor recovery in patients. Conversely, a neuroprotective effect is observed in animals subjected to acute sleep deprivation (SD) before ischemia. This neuroprotection is associated with an increase of the sleep, melanin concentrating hormone (MCH) and orexin/hypocretin (OX) systems. This study aims to 1) assess the relationship between sleep and recovery; 2) test the association between MCH and OX systems with the pathological mechanisms of stroke...
2017: PloS One
https://www.readbyqxmd.com/read/28039192/orexin-signaling-in-rostral-lateral-hypothalamus-and-nucleus-accumbens-shell-in-the-control-of-spontaneous-physical-activity-in-high-and-low-activity-rats
#14
Claudio Esteban Perez-Leighton, Morgan R Little, Martha K Grace, Charles J Billington, Catherine M Kotz
Spontaneous physical activity (SPA) describes activity outside of formal exercise and shows large inter-individual variability. The hypothalamic orexin/hypocretin peptides are key regulators of SPA. Orexins drive SPA within multiple brain sites, including rostral lateral hypothalamus (LH) and nucleus accumbens shell (NAcSh). Rats with high basal SPA (high activity, HA) show higher orexin mRNA expression and SPA after injection of orexin-A in rostral LH compared to low activity (LA) rats. Here we explored the contribution of orexin signaling in rostral LH and NAcSh to the HA/LA phenotype...
December 30, 2016: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28028605/neuropeptide-systems-and-new-treatments-for-nicotine-addiction
#15
REVIEW
Adriaan W Bruijnzeel
RATIONALE: The mildly euphoric and cognitive enhancing effects of nicotine play a role in the initiation of smoking, while dysphoria and anxiety associated with smoking cessation contribute to relapse. After the acute withdrawal phase, smoking cues, a few cigarettes (i.e., lapse), and stressors can cause relapse. Human and animal studies have shown that neuropeptides play a critical role in nicotine addiction. OBJECTIVES: The goal of this paper is to describe the role of neuropeptide systems in the initiation of nicotine intake, nicotine withdrawal, and the reinstatement of extinguished nicotine seeking...
December 28, 2016: Psychopharmacology
https://www.readbyqxmd.com/read/28025809/the-human-orexin-hypocretin-receptor-crystal-structures
#16
Jie Yin, Daniel M Rosenbaum
The human orexin/hypocretin receptors (hOX1R and hOX2R) are G protein-coupled receptors (GPCRs) that mediate the diverse functions of the orexin/hypocretin neuropeptides. Orexins/hypocretins produced by neurons in the lateral hypothalamus stimulate their cognate GPCRs in multiple regions of the central nervous system to control sleep and arousal, circadian rhythms, metabolism, reward pathways, and other behaviors. Dysfunction of orexin/hypocretin signaling is associated with human disease, and the receptors are active targets in a number of therapeutic areas...
December 27, 2016: Current Topics in Behavioral Neurosciences
https://www.readbyqxmd.com/read/28012092/the-hypocretin-orexin-neuronal-networks-in-zebrafish
#17
Idan Elbaz, Talia Levitas-Djerbi, Lior Appelbaum
The hypothalamic Hypocretin/Orexin (Hcrt) neurons secrete two Hcrt neuropeptides. These neurons and peptides play a major role in the regulation of feeding, sleep wake cycle, reward-seeking, addiction, and stress. Loss of Hcrt neurons causes the sleep disorder narcolepsy. The zebrafish has become an attractive model to study the Hcrt neuronal network because it is a transparent vertebrate that enables simple genetic manipulation, imaging of the structure and function of neuronal circuits in live animals, and high-throughput monitoring of behavioral performance during both day and night...
December 24, 2016: Current Topics in Behavioral Neurosciences
https://www.readbyqxmd.com/read/28012091/hypocretins-and-arousal
#18
Shi-Bin Li, William J Giardino, Luis de Lecea
How the brain controls vigilance state transitions remains to be fully understood. The discovery of hypocretins, also known as orexins, and their link to narcolepsy has undoubtedly allowed us to advance our knowledge on key mechanisms controlling the boundaries and transitions between sleep and wakefulness. Lack of function of hypocretin neurons (a relatively simple and non-redundant neuronal system) results in inappropriate control of sleep states without affecting the total amount of sleep or homeostatic mechanisms...
December 24, 2016: Current Topics in Behavioral Neurosciences
https://www.readbyqxmd.com/read/28012090/a-decade-of-orexin-hypocretin-and-addiction-where-are-we-now
#19
Morgan H James, Stephen V Mahler, David E Moorman, Gary Aston-Jones
One decade ago, our laboratory provided the first direct evidence linking orexin/hypocretin signaling with drug seeking by showing that activation of these neurons promotes conditioned morphine-seeking behavior. In the years since, contributions from many investigators have revealed roles for orexins in addiction for all drugs of abuse tested, but only under select circumstances. We recently proposed that orexins play a fundamentally unified role in coordinating "motivational activation" under numerous behavioral conditions, and here we unpack this hypothesis as it applies to drug addiction...
December 24, 2016: Current Topics in Behavioral Neurosciences
https://www.readbyqxmd.com/read/27997037/descending-projections-from-the-basal-forebrain-to-the-orexin-neurons-in-mice
#20
Lindsay J Agostinelli, Loris L Ferrari, Carrie E Mahoney, Takatoshi Mochizuki, Bradford B Lowell, Elda Arrigoni, Thomas E Scammell
The orexin (hypocretin) neurons play an essential role in promoting arousal, and loss of the orexin neurons results in narcolepsy, a condition characterized by chronic sleepiness and cataplexy. The orexin neurons excite wake-promoting neurons in the basal forebrain (BF), and a reciprocal projection from the BF back to the orexin neurons may help promote arousal and motivation. The BF contains at least three different cell types (cholinergic, glutamatergic, and GABAergic neurons) across its different regions (medial septum, diagonal band, magnocellular preoptic area, and substantia innominata)...
December 20, 2016: Journal of Comparative Neurology
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