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Russell Rosenberg, Max Hirshkowitz, David M Rapoport, Meir Kryger
Excessive daytime sleepiness (EDS) is a common complaint in the general population, which may be associated with a wide range of sleep disorders and other medical conditions. Narcolepsy is a sleep disorder characterized primarily by EDS, which involves a substantial burden of illness but is often overlooked or misdiagnosed. In addition to identifying low cerebrospinal fluid (CSF) hypocretin (orexin) levels, evaluation for narcolepsy requires in-laboratory polysomnography (PSG). Polysomnography is the gold standard for diagnosis of obstructive sleep apnea (OSA) as well as other sleep disorders...
January 28, 2019: Sleep Medicine
Katarzyna Palus-Chramiec, Lukasz Chrobok, Mariusz Kepczynski, Marian Henryk Lewandowski
Orexins/hypocretins are hypothalamic neuropeptides that have a variety of functions, including maintenance of arousal, control over the sleep/wake cycle, reward and feeding. Accumulating evidence links orexins to the time-keeping system with a documented action in the master clock - the suprachiasmatic nucleus. The intergeniculate leaflet (IGL) is a thalamic structure with the well-known function of collecting photic and nonphotic cues to adjust the rhythm of the suprachiasmatic nucleus to changing environmental conditions...
February 25, 2019: European Journal of Neuroscience
Steven J Simmons, Taylor A Gentile
Cocaine abuse remains a pervasive public health problem, and treatments thus far have proven ineffective for long-term abstinence maintenance. Intensive research on the neurobiology underlying drug abuse has led to the consideration of many candidate transmitter systems to target for intervention. Among these, the hypocretin/orexin (hcrt/ox) neuropeptide system holds largely untapped yet clinically viable therapeutic potential. Hcrt/ox originates from the hypothalamus and projects widely across the mammalian central nervous system to produce neuroexcitatory actions via two excitatory G-protein coupled receptor subtypes...
February 20, 2019: Brain Research
M Kiezun, K Dobrzyn, E Rytelewska, K Kisielewska, M Gudelska, K Szeszko, E Zaobidna, K Bors, J Wyrebek, A Mykytiuk, T Kaminski, N Smolinska
Orexin A and B (OXA, OXB) are hypothalamic neuropeptides acting via two receptors, type 1 (OX1R) and 2 (OX2R). Orexins, also known as hypocretins, take part in a common endocrine system regulating metabolism and reproductive functions. Changes in the orexin system expression during the estrous cycle and pregnancy suggest dependence on the local hormonal milieu. Estrogens are the key hormones controlling reproductive functions, including maternal recognition of pregnancy and implantation. We hypothesize that estrogens may affect orexin system expression in the early pregnant uterus...
January 4, 2019: Domestic Animal Endocrinology
Natasja Wulff Pedersen, Anja Holm, Nikolaj Pagh Kristensen, Anne-Mette Bjerregaard, Amalie Kai Bentzen, Andrea Marion Marquard, Tripti Tamhane, Kristoffer Sølvsten Burgdorf, Henrik Ullum, Poul Jennum, Stine Knudsen, Sine Reker Hadrup, Birgitte Rahbek Kornum
Narcolepsy Type 1 (NT1) is a neurological sleep disorder, characterized by the loss of hypocretin/orexin signaling in the brain. Genetic, epidemiological and experimental data support the hypothesis that NT1 is a T-cell-mediated autoimmune disease targeting the hypocretin producing neurons. While autoreactive CD4+  T cells have been detected in patients, CD8+  T cells have only been examined to a minor extent. Here we detect CD8+  T cells specific toward narcolepsy-relevant peptides presented primarily by NT1-associated HLA types in the blood of 20 patients with NT1 as well as in 52 healthy controls, using peptide-MHC-I multimers labeled with DNA barcodes...
February 19, 2019: Nature Communications
Cameron S McAlpine, Máté G Kiss, Sara Rattik, Shun He, Anne Vassalli, Colin Valet, Atsushi Anzai, Christopher T Chan, John E Mindur, Florian Kahles, Wolfram C Poller, Vanessa Frodermann, Ashley M Fenn, Annemijn F Gregory, Lennard Halle, Yoshiko Iwamoto, Friedrich F Hoyer, Christoph J Binder, Peter Libby, Mehdi Tafti, Thomas E Scammell, Matthias Nahrendorf, Filip K Swirski
Sleep is integral to life1 . Although insufficient or disrupted sleep increases the risk of multiple pathological conditions, including cardiovascular disease2 , we know little about the cellular and molecular mechanisms by which sleep maintains cardiovascular health. Here we report that sleep regulates haematopoiesis and protects against atherosclerosis in mice. We show that mice subjected to sleep fragmentation produce more Ly-6Chigh monocytes, develop larger atherosclerotic lesions and produce less hypocretin-a stimulatory and wake-promoting neuropeptide-in the lateral hypothalamus...
February 13, 2019: Nature
Jaanus Harro, Kariina Laas, Diva Eensoo, Triin Kurrikoff, Katre Sakala, Mariliis Vaht, Jüri Parik, Jarek Mäestu, Toomas Veidebaum
Orexins, alternatively called hypocretins, are neuropeptides with crucial role in maintaining wakefulness. The orexin system is thought to mediate a coordinated defense response but thus far investigated from the flight, but never fight, response perspective. An HCRTR1 gene variant (rs2271933 G > A) leading to amino acid substitution (Ile408Val) has been associated with migraine and mood disorders. We genotyped, and assessed aggressive behaviour in both birth cohorts (n = 655 and 583) of the Estonian Children Personality Behaviour and Health Study (ECPBHS)...
February 10, 2019: Neuropharmacology
Sebastian C Holst, Esther Werth, Hans-Peter Landolt
Pharmacotherapy of Sleep-Wake Disorders Abstract. Sleep is a complex behavior, coordinated by many different brain regions and neurotransmitters. These neurochemical systems can be pharmacologically influenced to modulate wakefulness and sleep. Excessive daytime sleepiness (EDS) is often treated with dopaminergic drugs, which in mild cases range from caffeine via (ar)modafinil to amphetamine derivatives. Tricyclic antidepressants and melatonin-based drugs are also used to promote alertness, but to a lesser extent...
January 2019: Praxis
Noriaki Sakai, Mari Matsumura, Ling Lin, Emmanuel Mignot, Seiji Nishino
Narcolepsy is a chronic sleep disorder caused by a loss of hypocretin (hcrt) neurons in the hypothalamus. Cerebrospinal fluid (CSF) hcrt-1 measurement has been well established as a gold standard of narcolepsy diagnosis, although some portions of narcoleptic patients show normal hcrt-1 levels. We aimed to examine peptide degradation of hcrt-1 and its abnormality in the CSF of patients by using high performance liquid chromatography (HPLC) followed by radioimmunoassay (RIA). CSF was collected from healthy controls, narcoleptic patients of type 1 with hcrt-1 deficiency, type 1 with normal hcrt-1 level, and type 2 with normal hcrt-1 level...
January 24, 2019: Scientific Reports
Mink Sebastian Schinkelshoek, Gert Jan Lammers, Rolf Fronczek
No abstract text is available yet for this article.
January 21, 2019: Sleep
Alessia Montesano, Mario Baumgart, Luigi Avallone, Luciana Castaldo, Carla Lucini, Eva Terzibasi Tozzini, Alessandro Cellerino, Livia D'Angelo, Paolo de Girolamo
Orexin A (OXA) and neuropeptide Y (NPY) are two hypothalamic neuropeptides involved in the regulation of feeding behaviour and food intake in all vertebrates. Accumulating evidences document that they undergo age-related modifications, with consequences on metabolism, sleep/wake disorders and progression of neurodegenerations. The present study addressed the age related changes in expression and distribution of orexin A (its precursor is also known as hypocretin - HCRT) and NPY, and their regulation by food intake in the short lived vertebrate model Nothobranchius furzeri...
January 21, 2019: Journal of Comparative Neurology
Carmen Fourier, Caroline Ran, Anna Steinberg, Christina Sjöstrand, Elisabet Waldenlind, Andrea Carmine Belin
OBJECTIVE: The purpose of this study was to investigate the HCRTR2 gene variants rs3122156, rs2653342, and rs2653349 in a large homogenous Swedish case-control cohort in order to further evaluate the possible contribution of HCRTR2 to cluster headache. BACKGROUND: Cluster headache is a severe neurovascular disorder and the pathophysiology is not yet fully understood. Due to striking circadian and circannual patterns of this disease, the hypothalamus has been a research focus in cluster headache...
January 16, 2019: Headache
Taku Miyagawa, Katsushi Tokunaga
Narcolepsy is a term that was initially coined by Gélineáu in 1880 and is a chronic neurological sleep disorder that manifests as a difficulty in maintaining wakefulness and sleep for long periods. Currently, narcolepsy is subdivided into two types according to the International Classification of Sleep Disorders, 3rd edition: narcolepsy type 1 (NT1) and narcolepsy type 2 (NT2). NT1 is characterized by excessive daytime sleepiness, cataplexy, hypnagogic hallucinations, and sleep paralysis and is caused by a marked reduction in neurons in the hypothalamus that produce orexin (hypocretin), which is a wakefulness-associated neuropeptide...
2019: Human Genome Variation
Sebjørg Elizabeth Hesla Nordstrand, Berit Hjelde Hansen, Terje Rootwelt, Tor-Ivar Karlsen, David Swanson, Kristian Bernhard Nilsen, Stine Knudsen
Study Objectives: Several studies have reported psychiatric comorbidity in patients with narcolepsy type 1 (NC1). The primary aim of this study was to explore the extent of psychiatric symptoms in a cohort of Norwegian NC1 patients, most of whom were H1N1-vaccinated. We also wanted to explore possible causes of the psychiatric symptoms seen in NC1. Methods: Cross-sectional study. Psychiatric symptoms were assessed by the Achenbach System of Empirically Based Assessment (ASEBA) Child Behavior Check List (CBCL) in children and by Adult Self Report (ASR) in adults...
January 12, 2019: Sleep
Mujgan Cengiz, Vilson Karaj, Nese Kocabasoğlu, Gokcen Gozubatik-Celik, Ahmet Dirican, Burcu Bayoglu
OBJECTIVE: Orexins (hypocretins) are neuropeptides expressed in hypothalamic neurons and have regulatory roles in feeding/drinking behaviours, endocrine functions and sleep/wakefulness state. Major depressive disorder (MDD) is a major mood disorder and neurotransmitter dysfunction in hypothalamic neurons may have roles in its formation. Hence, we conducted experiments to determine whether orexin receptor 1 and 2 (Orx1 , Orx2 ) genes were associated with MDD development. METHODS: Seventy-five MDD patients and 87 healthy controls were enrolled for the study...
December 31, 2018: International Journal of Psychiatry in Clinical Practice
Cliff H Summers, Jazmine D W Yaeger, Clarissa D Staton, David H Arendt, Tangi R Summers
Hypothalmic orexin/hypocretin (Orx) neurons in the lateral and dorsomedial perifornical region (LH-DMH/PeF) innervate broadly throughout the brain, and receive similar inputs. This wide distribution, as well as two Orx peptides (OrxA and OrxB ) and two Orx receptors (Orx1 and Orx2 ) allow for functionally related but distinctive behavioral outcomes, that include arousal, sleep-wake regulation, food seeking, metabolism, feeding, reward, addiction, and learning. These are all motivational functions, and tie the orexin systems to anxiety and depression as well...
December 24, 2018: Brain Research
C Schiappa, S Scarpelli, A D'Atri, M Gorgoni, Luigi De Gennaro
Narcolepsy is a chronic sleep disorder characterized by excessive daytime sleepiness, cataplexy, hypnagogic hallucinations, and sleep paralysis. This disease affects significantly the overall patient functioning, interfering with social, work, and affective life. Some symptoms of narcolepsy depend on emotional stimuli; for instance, cataplectic attacks can be triggered by emotional inputs such as laughing, joking, a pleasant surprise, and also anger. Neurophysiological and neurochemical findings suggest the involvement of emotional brain circuits in the physiopathology of cataplexy, which seems to depending on the dysfunctional interplay between the hypothalamus and the amygdala associated with an alteration of hypocretin levels...
December 26, 2018: Behavioral and Brain Functions: BBF
Lucie Barateau, Régis Lopez, Sofiene Chenini, Elisa Evangelista, Meriem Benkiran, Denis Mariano-Goulart, Isabelle Jaussent, Yves Dauvilliers
OBJECTIVE: To compare cardiac sympathetic adrenergic nerve activity in patients with narcolepsy type 1 (NT1) and controls using 123 I-MIBG myocardial scintigraphy, and to determine the clinical and neurophysiological variables associated with 123 I-MIBG scintigraphy results in NT1. METHODS: Fifty-six NT1 patients and 91 controls without neurological diseases underwent a cardiac scintigraphy. MIBG uptake was quantified by delayed heart/mediastinum (H/M) ratio. Clinical, neurophysiological and biological determinants of a low H/M were assessed in NT1...
December 6, 2018: Clinical Neurophysiology: Official Journal of the International Federation of Clinical Neurophysiology
Yuki C Saito, Natsuko Tsujino, Manabu Abe, Maya Yamazaki, Kenji Sakimura, Takeshi Sakurai
Neurons expressing neuropeptide orexins (hypocretins) in the lateral hypothalamus (LH) and serotonergic neurons in the dorsal raphe nucleus (DR) both play important roles in the regulation of sleep/wakefulness states, and show similar firing patterns across sleep/wakefulness states. Orexin neurons send excitatory projections to serotonergic neurons in the DR, which express both subtypes of orexin receptors (Mieda et al., 2011), while serotonin (5-HT) potently inhibits orexin neurons through activation of 5HT1A receptors (5HT1ARs)...
2018: Frontiers in Neuroscience
Carrie E Mahoney, Andrew Cogswell, Igor J Koralnik, Thomas E Scammell
Narcolepsy is the most common neurological cause of chronic sleepiness. The discovery about 20 years ago that narcolepsy is caused by selective loss of the neurons producing orexins (also known as hypocretins) sparked great advances in the field. Here, we review the current understanding of how orexin neurons regulate sleep-wake behaviour and the consequences of the loss of orexin neurons. We also summarize the developing evidence that narcolepsy is an autoimmune disorder that may be caused by a T cell-mediated attack on the orexin neurons and explain how these new perspectives can inform better therapeutic approaches...
December 13, 2018: Nature Reviews. Neuroscience
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