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https://www.readbyqxmd.com/read/29220370/absence-of-anti-hypocretin-receptor-2-autoantibodies-in-post-pandemrix-narcolepsy-cases
#1
Guo Luo, Ling Lin, Louis Jacob, Mélodie Bonvalet, Aditya Ambati, Giuseppe Plazzi, Fabio Pizza, Ryan Leib, Christopher M Adams, Markku Partinen, Emmanuel Jean-Marie Mignot
BACKGROUND: A recent publication suggested molecular mimicry of a nucleoprotein (NP) sequence from A/Puerto Rico/8/1934 (PR8) strain, the backbone used in the construction of the reassortant strain X-179A that was used in Pandemrix® vaccine, and reported on anti-hypocretin (HCRT) receptor 2 (anti-HCRTR2) autoantibodies in narcolepsy, mostly in post Pandemrix® narcolepsy cases (17 of 20 sera). In this study, we re-examined this hypothesis through mass spectrometry (MS) characterization of Pandemrix®, and two other pandemic H1N1 (pH1N1)-2009 vaccines, Arepanrix® and Focetria®, and analyzed anti-HCRTR2 autoantibodies in narcolepsy patients and controls using three independent strategies...
2017: PloS One
https://www.readbyqxmd.com/read/29207107/modular-organization-of-a-hypocretin-gene-minimal-promoter
#2
Adriana Sánchez-García, Griselda A Cabral-Pacheco, Viviana C Zomosa-Signoret, Rocío Ortiz-López, Alberto Camacho, Paulo M Tabera-Tarello, José A Garnica-López, Román Vidaltamayo
Orexins or hypocretins are neurotransmitters produced by a small population of neurons in the lateral hypothalamus. This family of peptides modulates sleep‑wake cycle, arousal and feeding behaviors; however, the mechanisms regulating their expression remain to be fully elucidated. There is an interest in defining the key molecular elements in orexin regulation, as these may serve to identify targets for generating novel therapies for sleep disorders, obesity and addiction. Our previous studies showed that the expression of orexin was decreased in mice carrying null‑mutations of the transcription factor early B‑cell factor 2 (ebf2) and that the promoter region of the prepro‑orexin (Hcrt) gene contained two putative ebf‑binding sites, termed olf‑1 sites...
November 22, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29198301/the-mslt-is-repeatable-in-narcolepsy-type-1-but-not-narcolepsy-type-2-a-retrospective-patient-study
#3
Chad Ruoff, Fabio Pizza, Lynn Marie Trotti, Karel Sonka, Stefano Vandi, Joseph Cheung, Swaroop Pinto, Mali Einen, Narong Simakajornboon, Fang Han, Paul Peppard, Sona Nevsimalova, Giuseppe Plazzi, David Rye, Emmanuel Mignot
STUDY OBJECTIVES: To examine repeatability of Multiple Sleep Latency Test (MSLT) results in narcolepsy type 1 (NT1) and narcolepsy type 2 (NT2) according to the criteria of the International Classification of Sleep Disorders, Third Edition (ICSD-3). METHODS: Repeatability of the MSLT was retrospectively evaluated in NT1 (n = 60) and NT2 (n = 54) cases, and controls (n = 15). All subjects had documented HLA-DQB1*06:02 status and/or hypocretin-1 levels from cerebrospinal fluid...
November 29, 2017: Journal of Clinical Sleep Medicine: JCSM: Official Publication of the American Academy of Sleep Medicine
https://www.readbyqxmd.com/read/29195824/pseudotumor-cerebri-syndrome-in-a-patient-with-narcolepsy-type-1
#4
Thomas Rossor, Ming Lim, Kirandeep VanDenEshof, Paul Gringras
Type 1 narcolepsy (NT1) is a chronic primary disorder of hypersomnolence characterized by excessive daytime sleepiness, cataplexy, sleep paralysis, hypnagogic hallucinations and disrupted nocturnal sleep. NT1 is linked to hypothalamic hypocretin deficiency, strongly associated with Human Leukocyte Antigen (HLA) marker DQB1*06:02 and of probable autoimmune origin. NT1 is usually associated with increased rates of overweight and obesity, and sometimes with increases in overnight blood pressure and increased rates of hypoventilation with raised CO2 levels overnight...
November 21, 2017: European Journal of Paediatric Neurology: EJPN
https://www.readbyqxmd.com/read/29186205/narcolepsy-susceptibility-gene-ccr3-modulates-sleep-wake-patterns-in-mice
#5
Hiromi Toyoda, Yoshiko Honda, Susumu Tanaka, Taku Miyagawa, Makoto Honda, Kazuki Honda, Katsushi Tokunaga, Tohru Kodama
Narcolepsy is caused by the loss of hypocretin (Hcrt) neurons and is associated with multiple genetic and environmental factors. Although abnormalities in immunity are suggested to be involved in the etiology of narcolepsy, no decisive mechanism has been established. We previously reported chemokine (C-C motif) receptor 3 (CCR3) as a novel susceptibility gene for narcolepsy. To understand the role of CCR3 in the development of narcolepsy, we investigated sleep-wake patterns of Ccr3 knockout (KO) mice. Ccr3 KO mice exhibited fragmented sleep patterns in the light phase, whereas the overall sleep structure in the dark phase did not differ between Ccr3 KO mice and wild-type (WT) littermates...
2017: PloS One
https://www.readbyqxmd.com/read/29180747/accumbal-d2-cells-orchestrate-innate-risk-avoidance-according-to-orexin-signals
#6
Craig Blomeley, Celia Garau, Denis Burdakov
Excitation of accumbal D2 cells governs vital actions, including avoidance of learned risks, but the origins of this excitation and roles of D2 cells in innate risk-avoidance are unclear. Hypothalamic neurons producing orexins (also called hypocretins) enhance innate risk-avoidance via poorly understood neurocircuits. We describe a direct orexin→D2 excitatory circuit and show that D2 cell activity is necessary for orexin-dependent innate risk-avoidance in mice, thus revealing an unsuspected hypothalamus-accumbens interplay in action selection...
November 27, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/29163002/serotonin-coordinates-responses-to-social-stress-what-we-can-learn-from-fish
#7
REVIEW
Tobias Backström, Svante Winberg
Social interaction is stressful and subordinate individuals are often subjected to chronic stress, which greatly affects both their behavior and physiology. In teleost fish the social position of an individual may have long-term effects, such as effects on migration, age of sexual maturation or even sex. The brain serotonergic system plays a key role in coordinating autonomic, behavioral and neuroendocrine stress responses. Social subordination results in a chronic activation of the brain serotonergic system an effect, which seems to be central in the subordinate phenotype...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29129795/orexin-a-hypocretin-1-immunoreactivity-in-the-lateral-hypothalamus-is-reduced-in-genetically-obese-but-not-in-diet-induced-obese-mice
#8
J Antonio González, Jochen H M Prehn
The mechanisms that link diet and body weight are not fully understood. A diet high in fat often leads to obesity, and this in part is the consequence of diet-induced injury to specific hypothalamic nuclei. It has been suggested that a diet high in fat leads to cell loss in the lateral hypothalamus, which contains specific populations of neurons that are essential for regulating energy homoeostasis; however, we do not know which cell types are affected by the diet. We studied the possibility that high-fat diet leads to a reduction in orexin-A/hypocretin-1 (Hcrt1) and/or melanin-concentrating hormone (MCH) immunoreactivity in the lateral hypothalamus...
November 10, 2017: Neuroscience
https://www.readbyqxmd.com/read/29107703/orexin-hypocretin-treatment-restores-hippocampal-dependent-memory-in-orexin-deficient-mice
#9
Vijayakumar Mavanji, Tammy A Butterick, Cayla M Duffy, Joshua P Nixon, Charles J Billington, Catherine M Kotz
Orexin A is produced in neurons of the lateral, perifornical and dorsomedial regions of the lateral hypothalamic area, which then project widely throughout the central nervous system to regulate arousal state, sleep-wake architecture, energy homeostasis and cognitive processes. Disruption of orexin signaling leads to sleep disturbances and increased body mass index, but recent studies also indicate that orexin neuron activation improves learning and memory. We hypothesized that hippocampal orexin receptor activation improves memory...
October 28, 2017: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/29107089/orexins-hypocretins-and-sex
#10
EDITORIAL
Olaf Jöhren
No abstract text is available yet for this article.
October 26, 2017: Peptides
https://www.readbyqxmd.com/read/29096748/organic-chromium-modifies-the-expression-of-orexin-and-glucose-transporters-of-ovarian-in-heat-stressed-laying-hens
#11
O Ozdemir, M Tuzcu, N Sahin, C Orhan, Z Tuzcu, K Sahin
In this study, the effect of the supplemental organic chromium (Cr) forms on the expression of ovarian orexin(hypocretin), glucose transporters (GLUTs), heat shock proteins (HSPs) andnuclear factor-kappaB (NF-κB)were investigated in laying hens (HS). Laying hens (n=1800; 16-wk-old; Lohmann LSL-Lite) were allocated to 6 random groups according to a 2 × 3 factorial trial scheme with two different environmental temperatures [Thermoneutral (TN groups; at either 22±2 °C 24 h/d)  and heat stress (HS groups; at 34±2 °C for 8 h/d, 08:00 to 17:00 h, followed by 22°C for 16 h for a period of 12 wks)], andhens reared under both environmental conditions were fed either a basal diet or the basal diet supplemented with 1...
October 31, 2017: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/29056152/orexin-hypocretin-system-role-in-food-and-drug-overconsumption
#12
Jessica R Barson, Sarah F Leibowitz
The neuropeptide orexin/hypocretin (OX), while largely transcribed within the hypothalamus, is released throughout the brain to affect complex behaviors. Primarily through the hypothalamus itself, OX homeostatically regulates adaptive behaviors needed for survival, including food intake, sleep-wake regulation, mating, and maternal behavior. However, through extrahypothalamic limbic brain regions, OX promotes seeking and intake of rewarding substances of abuse, like palatable food, alcohol, nicotine, and cocaine...
2017: International Review of Neurobiology
https://www.readbyqxmd.com/read/29054286/functional-roles-of-orexin-hypocretin-receptors-in-reward-circuit
#13
Abbas Haghparast, Zahra Fatahi, Reza Arezoomandan, Sara Karimi, Zahra Taslimi, Shahram Zarrabian
Since its first discovery in 1998, it has become clear that the orexinergic system plays an important role in regulating a number of functions including food, sex, social connections, and most prominently reward-related behaviors. Orexinergic neurons in the lateral hypothalamus project extensively to other brain areas, two most important of which are the ventral tegmental area and the nucleus accumbens that are involved in reward processing. In this review, we have presented the work in our laboratory along with the work of others and have discussed the possible functions we can infer from the research...
2017: Progress in Brain Research
https://www.readbyqxmd.com/read/29038792/neuroanatomical-relationships-between-orexin-hypocretin-containing-neurons-nerve-fibers-and-nicotine-induced-c-fos-activated-cells-of-the-reward-addiction-neurocircuitry
#14
Ozra Dehkordi, Jed E Rose, Martha I Dávila-García, Richard M Millis, Samar Ali Mirzaei, Kebreten F Manaye, Annapurni Jayam-Trouth
Orexin/hypocretin-containing neurons in lateral hypothalamus (LH) are implicated in the neurobiology of nicotine addiction. However, the neuroanatomical relationships between orexin-neurons/nerve fibers and nicotine-activated cells within the reward-addiction neurocircuitry is not known. In the present study in mice, we first used c-Fos immunohistochemistry to identify CNS cells stimulated by an acute single injection of nicotine (NIC, 2 mg/kg, IP). Sequential double-labelling was then performed to identify the location of orexin-containing neurons and nerve fibers with respect to NIC-induced c-Fos activated cells and/or tyrosine hydroxylase (TH) immunoreactive (IR) cells of the mesocorticolimbic reward-addiction pathways...
August 2017: Journal of Alcoholism and Drug Dependence
https://www.readbyqxmd.com/read/29029348/dysregulation-of-sleep-behavioral-states-in-narcolepsy
#15
Sarah F Schoch, Esther Werth, Rositsa Poryazova, Thomas E Scammell, Christian R Baumann, Lukas L Imbach
Study Objectives: Patients with narcolepsy suffer from poor maintenance of wakefulness and fragmented night sleep, but the underlying mechanism of sleep boundary dysregulation remains little understood. The goal of this study was to quantify abnormal sleep-wake regulation in narcolepsy patients. Methods: Using a model-based approach (state space analysis), we analyzed overnight EEG recordings in ten patients with narcolepsy type 1 and age- and gender-matched healthy control subjects...
October 5, 2017: Sleep
https://www.readbyqxmd.com/read/28991183/orexin-receptor-multimerization-versus-functional-interactions-neuropharmacological-implications-for-opioid-and-cannabinoid-signalling-and-pharmacogenetics
#16
Miles D Thompson, Takeshi Sakurai, Innocenzo Rainero, Mary C Maj, Jyrki P Kukkonen
Orexins/hypocretins are neuropeptides formed by proteolytic cleavage of a precursor peptide, which are produced by neurons found in the lateral hypothalamus. The G protein-coupled receptors (GPCRs) for these ligands, the OX₁ and OX₂ orexin receptors, are more widely expressed throughout the central nervous system. The orexin/hypocretin system has been implicated in many pathways, and its dysregulation is under investigation in a number of diseases. Disorders in which orexinergic mechanisms are being investigated include narcolepsy, idiopathic sleep disorders, cluster headache and migraine...
October 8, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28991006/autoimmunity-in-narcolepsy
#17
Melodie Bonvalet, Hanna M Ollila, Aditya Ambati, Emmanuel Mignot
PURPOSE OF REVIEW: Summarize the recent findings in narcolepsy focusing on the environmental and genetic risk factors in disease development. RECENT FINDINGS: Both genetic and epidemiological evidence point towards an autoimmune mechanism in the destruction of orexin/hypocretin neurons. Recent studies suggest both humoral and cellular immune responses in the disease development. SUMMARY: Narcolepsy is a severe sleep disorder, in which neurons producing orexin/hypocretin in the hypothalamus are destroyed...
November 2017: Current Opinion in Pulmonary Medicine
https://www.readbyqxmd.com/read/28975007/the-medical-and-economic-burden-of-narcolepsy-implications-for-managed-care
#18
REVIEW
Michael J Thorpy, George Hiller
BACKGROUND: The neurologic disorder narcolepsy results from dysregulation of the sleep-wake cycle and is primarily characterized by chronic, severely excessive daytime sleepiness and cataplexy, an emotionally induced muscle weakness. The prevalence of narcolepsy is approximately 0.05%, and onset generally occurs during the first 2 decades of life. Narcolepsy is believed to be an autoimmune disorder with destruction of hypocretin-producing neurons in the lateral hypothalamus. OBJECTIVES: To provide an enhanced understanding of narcolepsy and establish the need for early diagnosis and rapid initiation of effective treatment for patients with narcolepsy...
July 2017: American Health & Drug Benefits
https://www.readbyqxmd.com/read/28971565/hypocretin-receptor-1-knockdown-in-the-ventral-tegmental-area-attenuates-mesolimbic-dopamine-signaling-and-reduces-motivation-for-cocaine
#19
David L Bernstein, Preeti S Badve, Jessica R Barson, Caroline E Bass, Rodrigo A España
The hypocretin receptor 1 (HCRTr1) is a critical participant in the regulation of motivated behavior. Previous observations demonstrate that acute pharmacological blockade of HCRTr1 disrupts dopamine (DA) signaling and the motivation for cocaine when delivered systemically or directly into the ventral tegmental area (VTA). To further examine the involvement of HCRTr1 in regulating reward and reinforcement processing, we employed an adeno-associated virus to express a short hairpin RNA designed to knock down HCRTr1...
October 2, 2017: Addiction Biology
https://www.readbyqxmd.com/read/28966976/neurochemical-heterogeneity-among-lateral-hypothalamic-hypocretin-orexin-and-melanin-concentrating-hormone-neurons-identified-through-single-cell-gene-expression-analysis
#20
Laura E Mickelsen, Fredrick W Kolling, Brock R Chimileski, Akie Fujita, Carol Norris, Kun Chen, Craig E Nelson, Alexander C Jackson
The lateral hypothalamic area (LHA) lies at the intersection of multiple neural and humoral systems and orchestrates fundamental aspects of behavior. Two neuronal cell types found in the LHA are defined by their expression of hypocretin/orexin (Hcrt/Ox) and melanin-concentrating hormone (MCH) and are both important regulators of arousal, feeding, and metabolism. Conflicting evidence suggests that these cell populations have a more complex signaling repertoire than previously appreciated, particularly in regard to their coexpression of other neuropeptides and the machinery for the synthesis and release of GABA and glutamate...
September 2017: ENeuro
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