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Hypocretin

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https://www.readbyqxmd.com/read/28323938/loss-of-action-via-neurotensin-leptin-receptor-neurons-disrupts-leptin-and-ghrelin-mediated-control-of-energy-balance
#1
Juliette A Brown, Raluca Bugescu, Thomas Mayer, Adriana Gata-Garcia, Gizem Kurt, Hillary L Woodworth, Gina M Leinninger
The hormones ghrelin and leptin act via the lateral hypothalamic area (LHA) to modify energy balance but the underlying neural mechanisms remain unclear. We investigated how leptin and ghrelin engage LHA neurons to modify energy balance behaviors and whether there is any cross-talk between leptin and ghrelin-responsive circuits. We demonstrate that ghrelin activates LHA neurons expressing Hypocretin/Orexin (OX) to increase food intake. Leptin mediates anorectic actions via separate neurons expressing the long form of the leptin receptor (LepRb), many of which co-express the neuropeptide neurotensin (Nts); we refer to these as NtsLepRb neurons...
March 10, 2017: Endocrinology
https://www.readbyqxmd.com/read/28303403/hypocretin-orexin-and-plastic-adaptations-associated-with-drug-abuse
#2
Corey Baimel, Stephanie L Borgland
Dopamine neurons in the ventral tegmental area (VTA) are a critical part of the neural circuits that underlie reward learning and motivation. Dopamine neurons send dense projections throughout the brain and recent observations suggest that both the intrinsic properties and the functional output of dopamine neurons are dependent on projection target and are subject to neuromodulatory influences. Lateral hypothalamic hypocretin (also termed orexin) neurons project to the VTA and contain both hypocretin and dynorphin peptides in the same dense core vesicles suggesting they may be co-released...
March 17, 2017: Current Topics in Behavioral Neurosciences
https://www.readbyqxmd.com/read/28296947/the-dual-orexin-receptor-antagonist-tcs1102-does-not-affect-reinstatement-of-nicotine-seeking
#3
Shaun Yon-Seng Khoo, Gavan P McNally, Kelly J Clemens
The orexin/hypocretin system is important for appetitive motivation towards multiple drugs of abuse, including nicotine. Both OX1 and OX2 receptors individually have been shown to influence nicotine self-administration and reinstatement. Due to the increasing clinical use of dual orexin receptor antagonists in the treatment of disorders such as insomnia, we examined whether a dual orexin receptor antagonist may also be effective in reducing nicotine seeking. We tested the effect of intracerebroventricular (i...
2017: PloS One
https://www.readbyqxmd.com/read/28283054/orexin-hypocretin-central-amygdala-and-escalation-of-cocaine-intake
#4
Morgan H James, Gary Aston-Jones
No abstract text is available yet for this article.
April 1, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/28275716/genetic-analysis-of-histamine-signaling-in-larval-zebrafish-sleep
#5
Audrey Chen, Chanpreet Singh, Grigorios Oikonomou, David A Prober
Pharmacological studies in mammals and zebrafish suggest that histamine plays an important role in promoting arousal. However, genetic studies using rodents with disrupted histamine synthesis or signaling have revealed only subtle or no sleep/wake phenotypes. Studies of histamine function in mammalian arousal are complicated by its production in cells of the immune system and its roles in humoral and cellular immunity, which can have profound effects on sleep/wake states. To avoid this potential confound, we used genetics to explore the role of histamine in regulating sleep in zebrafish, a diurnal vertebrate in which histamine production is restricted to neurons in the brain...
January 2017: ENeuro
https://www.readbyqxmd.com/read/28272728/-regulation-of-the-phases-of-the-sleep-wakefulness-cycle-with-histamine
#6
REVIEW
A Diez-Garcia, M Garzon
Distributed neural networks in the brain sustain generation of wakefulness and two sleep states: non-REM sleep and REM sleep. These three behavioral states are jointly ingrained in a rhythmic sequence that constitutes the sleep-wakefulness cycle. This paper reviews and updates knowledge about the involvement of the histaminergic system in sleep-wakefulness cycle organization. Histaminergic neurons are exclusively located in the hypothalamic tuberomammillary nucleus, but are the source of a widespread projection system to many brain regions...
March 16, 2017: Revista de Neurologia
https://www.readbyqxmd.com/read/28250055/mapping-the-hypocretin-orexin-neuronal-system-an-unexpectedly-productive-journey
#7
Christelle Peyron, Thomas S Kilduff
Early in 1998, we (de Lecea et al., 1998) and others (Sakurai et al., 1998) described the same hypothalamic neuropeptides, respectively called the hypocretins or orexins, which were discovered using two different approaches. In December of that year, we published the subject of this commentary in the Journal of Neuroscience: a highly detailed anatomical description of the extensive axonal projections of the hypocretin/orexin neurons. Although the function of this system was unknown at the time, a large body of literature today attests that the hypocretin/orexin neuropeptides play important roles in multiple physiological functions, particularly in sleep/wake regulation...
March 1, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28235898/gabaergic-neurons-of-the-central-amygdala-promote-cataplexy
#8
Carrie E Mahoney, Lindsay J Agostinelli, Jessica N K Brooks, Bradford B Lowell, Thomas E Scammell
Narcolepsy is characterized by chronic sleepiness and cataplexy - sudden muscle paralysis triggered by strong, positive emotions. Narcolepsy is caused by a lack of orexin (hypocretin) signaling, but little is known about the neural mechanisms that mediate cataplexy. The amygdala regulates responses to rewarding stimuli and contains neurons active during cataplexy. In addition, lesions of the amygdala reduce cataplexy. As GABAergic neurons of the central nucleus of the amygdala (CeA) target brainstem regions known to regulate muscle tone, we hypothesized that these cells promote emotion-triggered cataplexy...
February 24, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28209438/excessive-daytime-sleepiness-in-a-patient-with-coexisting-myotonic-dystrophy-type-1-myasthenia-gravis-and-graves-disease
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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...
March 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
#18
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...
March 2017: Animal Reproduction Science
https://www.readbyqxmd.com/read/28087252/novel-method-for-evaluation-of-eye-movements-in-patients-with-narcolepsy
#19
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
#20
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
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