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Roberta Imperatore, Livia D'Angelo, Omid Safari, Hamidreza Ahmadniaye Motlagh, Fabiana Piscitelli, Paolo de Girolamo, Luigia Cristino, Ettore Varricchio, Vincenzo di Marzo, Marina Paolucci
Hypocretins/Orexins neuropeptides are known to regulate numerous physiological functions, such as energy homeostasis, food intake, sleep/wake cycle, arousal and wakefulness, in vertebrates. Previous studies on mice have revealed an intriguing orexins/endocannabinoids (ECs) signaling interaction at both structural and functional levels, with OX-A behaving as a strong enhancer of 2-arachydonoyl-glycerol (2-AG) biosynthesis. In this study, we describe, for the first time in the brain of zebrafish, the anatomical distribution and co-expression of orexin (OX-2R) and endocannabinoid (CB1R) receptors, suggesting a functional interaction...
2018: Frontiers in Neuroanatomy
Shi-Bin Li, Natalie Nevárez, William J Giardino, Luis de Lecea
Study Objectives: The present study investigated the function of Hypocretin (Hcrt or Orexin/OX) receptor antagonists in sleep modulation and memory function with optical methods in transgenic mice. Methods: We used Hcrt-IRES-Cre knock-in mice and AAV vectors expressing channelrhodopsin-2 (ChR2) to render Hcrt neurons sensitive to blue light stimulation. We optogenetically stimulated Hcrt neurons and measured latencies to wakefulness in the presence or absence of OX1/2R antagonists and Zolpidem...
July 27, 2018: Sleep
Karin Sofia Scherrer, Christa Relly, Annette Hackenberg, Christoph Berger, Paolo Paioni
RATIONALE: Despite the acknowledged importance of environmental risk factors in the etiology of narcolepsy, there is little research on this topic. HIV as a trigger for narcolepsy has not been systematically investigated. PATIENT CONCERNS: We describe a case of narcolepsy type 1 (NT1) in an adolescent with HIV infection presenting with increased daytime sleepiness and excessive weight gain. DIAGNOSES: NT1 was diagnosed according to the criteria of the third edition of the International Classification of Sleep Disorders (ICSD-3)...
July 2018: Medicine (Baltimore)
William J Giardino, Ada Eban-Rothschild, Daniel J Christoffel, Shi-Bin Li, Robert C Malenka, Luis de Lecea
Lateral hypothalamus (LH) neurons containing the neuropeptide hypocretin (HCRT; orexin) modulate affective components of arousal, but their relevant synaptic inputs remain poorly defined. Here we identified inputs onto LH neurons that originate from neuronal populations in the bed nuclei of stria terminalis (BNST; a heterogeneous region of extended amygdala). We characterized two non-overlapping LH-projecting GABAergic BNST subpopulations that express distinct neuropeptides (corticotropin-releasing factor, CRF, and cholecystokinin, CCK)...
August 2018: Nature Neuroscience
Manasi Iyer, Rachel A Essner, Bernhard Klingenberg, Matthew E Carter
Neurons in the lateral hypothalamic area that express hypocretin (Hcrt) neuropeptides help regulate many behaviors including wakefulness and reward seeking. These neurons project throughout the brain, including to neural populations that regulate wakefulness, such as the locus coeruleus (LC) and tuberomammilary nucleus (TMN), as well as to populations that regulate reward, such as the nucleus accumbens (NAc) and ventral tegmental area (VTA). To address the roles of Hcrt neurons in seemingly disparate behaviors, it has been proposed that Hcrt neurons can be anatomically subdivided into at least two distinct subpopulations: a "medial group" that projects to the LC and TMN, and a "lateral group" that projects to the NAc and VTA...
July 18, 2018: Journal of Comparative Neurology
Barbara Baldo, Sanaz Gabery, Rana Soylu-Kucharz, Rachel Y Cheong, Jo B Henningsen, Elisabet Englund, Catriona McLean, Deniz Kirik, Glenda Halliday, Åsa Petersén
AIMS: Metabolic dysfunction is involved in modulating the disease process in Huntington disease (HD) but the underlying mechanisms are not known. The aim of the present study was to investigate if the metabolic regulators sirtuins are affected in HD. METHODS: Quantitative real time polymerase chain reactions were used to assess levels of SIRT1-3 and downstream targets in postmortem brain tissue from HD patients and control cases as well as after selective hypothalamic expression of mutant huntingtin using recombinant adeno-associated viral vectors in mice...
July 18, 2018: Neuropathology and Applied Neurobiology
Hilde T Juvodden, Dag Alnæs, Martina J Lund, Ingrid Agartz, Ole A Andreassen, Espen Dietrichs, Per M Thorsby, Lars T Westlye, Stine Knudsen
Study Objectives: To assess white matter involvement in H1N1-vaccinated hypocretin deficient narcolepsy type 1 (NT1) patients compared with 1st degree relatives (a potential risk group), and healthy controls. Methods: We compared four diffusion tensor imaging-based microstructural indices (fractional anisotropy (FA), mean (MD), radial (RD), and axial diffusivity (AD)) in 57 NT1 patients (39 females, mean age 21.8 years, 51/57 H1N1-vaccinated, 57/57 HLA-DQB1*06:02-positive, 54/54 hypocretin-deficient), 54 1st degree relatives (29 females, mean age 19...
July 17, 2018: Sleep
Daniel Lozano, Agustín González, Jesús M López
Holosteans form a small group of actinopterygian fishes considered the sister group of teleosts. Despite this proximity to the biggest group of vertebrates, relatively few studies have been conducted to investigate the organization of the central nervous system of this group of fishes. In this study, the neuroanatomical distribution of orexin/hypocretin-like immunoreactive (OX-ir) cell bodies and fibers was analyzed in the brain of 3 representative species of the 2 orders of extant holosteans, the spotted gar Lepisosteus oculatus, the Florida gar Lepisosteus platyrhincus, and the bowfin Amia calva...
July 13, 2018: Brain, Behavior and Evolution
Chunmei Wang, Qinqin Wang, Bingyuan Ji, Yanyou Pan, Chao Xu, Baohua Cheng, Bo Bai, Jing Chen
Orexins, also known as hypocretins, are two neuropeptides secreted from orexin-containing neurons, mainly in the lateral hypothalamus (LH). Orexins orchestrate their effects by binding and activating two G-protein-coupled receptors (GPCRs), orexin receptor type 1 (OX1R) and type 2 (OX2R). Orexin/receptor pathways play vital regulatory roles in many physiological processes, especially feeding behavior, sleep-wake rhythm, reward and addiction and energy balance. Furthermore several reports showed that orexin/receptor pathways are involved in pathological processes of neurological diseases such as narcolepsy, depression, ischemic stroke, drug addiction and Alzheimer's disease (AD)...
2018: Frontiers in Molecular Neuroscience
Mariusz Sieminski, Jacek Szypenbejl, Eemil Partinen
PURPOSE OF REVIEW: The aim of this review was to summarize collected data on the role of orexin and orexin neurons in the control of sleep and blood pressure. RECENT FINDINGS: Although orexins (hypocretins) have been known for only 20 years, an impressive amount of data is now available regarding their physiological role. Hypothalamic orexin neurons are responsible for the control of food intake and energy expenditure, motivation, circadian rhythm of sleep and wake, memory, cognitive functions, and the cardiovascular system...
July 10, 2018: Current Hypertension Reports
Azadeh Sabetghadam, Agnieszka Grabowiecka-Nowak, Alan Kania, Anna Gugula, Ewa Blasiak, Tomasz Blasiak, Sherie Ma, Andrew L Gundlach, Anna Blasiak
The rat nucleus incertus (NI) contains GABA/peptide-projection neurons responsive to orexin (hypocretin)/orexin receptor-2 (OX2 ) signalling. Melanin-concentrating hormone (MCH) and orexin neurons often innervate and influence common target areas. Therefore, we assessed the relationship between these hypothalamic peptidergic systems and rat NI, by investigating the presence of an MCH innervation and MCH receptor-1 (MCH1 ) expression, and neurophysiological and behavioural effects of MCH c.f. orexin-A (OXA), within the NI...
September 1, 2018: Neuropharmacology
Ulf Kallweit, Claudio L A Bassetti, Michael Oberholzer, Rolf Fronczek, Mathieu Béguin, Matthias Strub, Gert Jan Lammers
BACKGROUND: There are increasing data suggesting the involvement of the immune system in narcolepsy. The co-occurrence of narcolepsy with other autoimmune disorders (including multiple sclerosis, MS) is rare. PATIENTS AND METHODS: International multicenter sleep center survey and literature review on narcolepsy with (NC) and without (NwC) cataplexy. RESULTS: A total of 26 patients (pts), 6 in the survey and 20 in the literature were found...
July 4, 2018: Journal of Neurology
Zhen Cai, Hehe Liu, Liyun Wang, Xinxin Li, Lili Bai, Xinmeng Gan, Liang Li, Chunchun Han
Hypocretin system is composed of hypocretins (hcrts) and their receptors (hcrtrs), which has multiple vital functions. Hypocretins work via hypocretin receptors and it is reported that functional differentiation occurred in hcrtrs. It is necessary to figure out the evolution process of hypocretin receptors. In our study, we adopt a comprehensive approach and various bioinformatics tools to analyse the evolution process of HCRTR gene family. It turns out that the second round of whole genome duplication in early vertebrate ancestry and the independent round in fish ancestry may contribute to the diversity of HCRTR gene family...
2018: BioMed Research International
Thomas C Thannickal, Joshi John, Ling Shan, Dick F Swaab, Ming-Fung Wu, Lalini Ramanathan, Ronald McGregor, Keng-Tee Chew, Marcia Cornford, Akihiro Yamanaka, Ayumu Inutsuka, Rolf Fronczek, Gert Jan Lammers, Paul F Worley, Jerome M Siegel
The changes in brain function that perpetuate opiate addiction are unclear. In our studies of human narcolepsy, a disease caused by loss of immunohistochemically detected hypocretin (orexin) neurons, we encountered a control brain (from an apparently neurologically normal individual) with 50% more hypocretin neurons than other control human brains that we had studied. We discovered that this individual was a heroin addict. Studying five postmortem brains from heroin addicts, we report that the brain tissue had, on average, 54% more immunohistochemically detected neurons producing hypocretin than did control brains from neurologically normal subjects...
June 27, 2018: Science Translational Medicine
Jeffrey A Miskoff, Moiuz Chaudhri
Narcolepsy is a sleep disorder that can manifest in childhood or adolescence by causing excessive sleepiness, hallucinations, sleep attacks, or cataplexy. There is often a significant delay in diagnosis with the mean time being 15 years from the onset of symptoms, which may lead to further exacerbations and a high comorbidity burden. Although narcolepsy is predominantly associated with loss of hypocretin (orexin), the role of genetics is poorly understood and, therefore, is complementary to the diagnosis but not confirmatory...
April 24, 2018: Curēus
Susan M Tyree, Jeremy C Borniger, Luis de Lecea
The lateral hypothalamus is comprised of a heterogeneous mix of neurons that serve to integrate and regulate sleep, feeding, stress, energy balance, reward, and motivated behavior. Within these populations, the hypocretin/orexin neurons are among the most well studied. Here, we provide an overview on how these neurons act as a central hub integrating sensory and physiological information to tune arousal and motivated behavior accordingly. We give special attention to their role in sleep-wake states and conditions of hyper-arousal, as is the case with stress-induced anxiety...
2018: Frontiers in Neurology
Renata C Cremaschi, Camila Hirotsu, Sergio Tufik, Fernando M Coelho
Narcolepsy is a rare sleep disorder classified in types 1 and 2. The co-morbidities of narcolepsy type 1, with hypocretin-1 deficiency, are established. Hypocretin-1 in the central and peripheral nervous systems regulates nociception and pain. However, the patients with narcolepsy type 2 have similar excessive daytime sleepiness and co-morbidities without elucidation. The objective of the study was to determine the frequency and the characteristic of chronic pain according to the type of narcolepsy. We also investigated the effect of the interaction between the nutritional status and the type of narcolepsy...
June 19, 2018: Journal of Sleep Research
Marta Kowalska, Magdalena Kapelusiak-Pielok, Teresa Grzelak, Ewa Wypasek, Wojciech Kozubski, Jolanta Dorszewska
Migraine is one of the most common primary headache disorders that affects 11% of the adult population. The disease is divided into two main clinical subtypes: migraine with aura (MA) and migraine without aura (MO). Both serotonergic and hypocretinergic systems are involved in the migraine pathomechanism. Polymorphisms in the serotonin transporter gene ( SLC6A4 ) and the hypocretin receptor 1 gene ( HCRTR1 ) may be risk factors for migraine development due to their ability to affect serotonin and hypocretin-1 (HCRT-1) concentrations...
2018: Frontiers in Molecular Neuroscience
Lucia Recinella, Annalisa Chiavaroli, Claudio Ferrante, Adriano Mollica, Giorgia Macedonio, Azzurra Stefanucci, Marilisa Pia Dimmito, Szabolcs Dvorácskó, Csaba Tömböly, Luigi Brunetti, Giustino Orlando, Sheila Leone
BACKGROUND: The endocannabinoid (eCB) system is strongly involved in the regulation of anxiety and feeding behavior. RVD-hemopressin(α) [RVD-hp(α)], a N-terminally extended form of hemopressin, is a negative allosteric modulator of the cannabinoid (CB) 1 receptor and a positive allosteric modulator of CB2 receptor which has been recently reported to exert anxiolytic/antidepressant and anorexigenic effects after peripheral administration in rats. Pharmacological evidences reported a possible link between brain hypocretin/orexin, monoamine and eCB systems, as regards appetite and emotional behavior control...
February 2, 2018: Pharmacological Reports: PR
David N Neubauer, Seithikurippu R Pandi-Perumal, David Warren Spence, Kenneth Buttoo, Jaime M Monti
Insomnia remains a common clinical concern that is associated with negative daytime consequences for patients and represents a significant public health problem for our society. Although a variety of therapies may be employed to treat insomnia, the use of medications has been a dominant approach. Regulatory agencies have now classified insomnia medications into 4 distinct pharmacodynamics classes. Medications with indications approved for insomnia treatment include benzodiazepine receptor agonists, a melatonin receptor agonist, a selective histamine receptor antagonist, and a dual orexin/hypocretin receptor antagonist...
2018: Journal of Central Nervous System Disease
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