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Hypocretin

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https://www.readbyqxmd.com/read/29624767/systemic-exertion-intolerance-disease-chronic-fatigue-syndrome-is-common-in-sleep-centre-patients-with-hypersomnolence-a-retrospective-pilot-study
#1
Caroline Maness, Prabhjyot Saini, Donald L Bliwise, Victoria Olvera, David B Rye, Lynn M Trotti
Symptoms of the central disorders of hypersomnolence extend beyond excessive daytime sleepiness to include non-restorative sleep, fatigue and cognitive dysfunction. They share much in common with myalgic encephalomyelitis/chronic fatigue syndrome, recently renamed systemic exertion intolerance disease, whose additional features include post-exertional malaise and orthostatic intolerance. We sought to determine the frequency and correlates of systemic exertion intolerance disease in a hypersomnolent population...
April 6, 2018: Journal of Sleep Research
https://www.readbyqxmd.com/read/29623725/an-overview-of-hypocretin-based-therapy-in-narcolepsy
#2
Shinichi Takenoshita, Noriaki Sakai, Yuhei Chiba, Mari Matsumura, Mai Yamaguchi, Seiji Nishino
Narcolepsy with cataplexy is most commonly caused by a loss of hypocretin/orexin peptide-producing neurons in the hypothalamus (i.e., Narcolepsy Type 1). Since hypocretin deficiency is assumed to be the main cause of narcoleptic symptoms, hypocretin replacement will be the most essential treatment for narcolepsy. Unfortunately, this option is still not available clinically. There are many potential approaches to replace hypocretin in the brain for narcolepsy such as intranasal administration of hypocretin peptides, developing small molecule hypocretin receptor agonists, hypocretin neuronal transplantation, transforming hypocretin stem cells into hypothalamic neurons, and hypocretin gene therapy...
April 6, 2018: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/29616340/dopamine-and-wakefulness-pharmacology-genetics-and-circuitry
#3
Jonathan P Wisor
Over the period of decades in the mid to late twentieth century, arousal-promoting functions were attributed to neuromodulators including serotonin, hypocretin, histamine, and noradrenaline. For some time, a relatively minor role in regulating sleep and wake states was ascribed to dopamine and the dopamine-producing cells of the ventral tegmental area, despite the fact that dopaminergic signaling is a major target, if not the primary target, for wake-promoting agents. In recent years, due to observations from human genetic studies, pharmacogenetic studies in animal models, and the increasingly sophisticated methods used to manipulate the nervous systems of experimental animals, it has become clear that dopaminergic signaling is central to the regulation of arousal...
April 4, 2018: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/29580887/neuroimaging-correlates-of-narcolepsy-with-cataplexy-a-systematic-review
#4
REVIEW
Masataka Wada, Masaru Mimura, Yoshihiro Noda, Shotaro Takasu, Eric Plitman, Makoto Honda, Akiyo Natsubori, Kamiyu Ogyu, Ryosuke Tarumi, Ariel Graff-Guerrero, Shinichiro Nakajima
Recent developments in neuroimaging techniques have advanced our understanding of biological mechanisms underpinning narcolepsy. We used MEDLINE to retrieve neuroimaging studies to compare patients with narcolepsy and healthy controls. Thirty-seven studies were identified and demonstrated several replicated abnormalities: (1) gray matter reductions in superior frontal, superior and inferior temporal, and middle occipital gyri, hypothalamus, amygdala, insula, hippocampus, cingulate cortex, thalamus, and nucleus accumbens, (2) decreased fractional anisotropy in white matter of fronto-orbital and cingulate area, (3) reduced brain metabolism or cerebral blood flow in middle and superior frontal, and cingulate cortex (4) increased activity in inferior frontal gyri, insula, amygdala, and nucleus accumbens, and (5) N-acetylaspartate/creatine-phosphocreatine level reduction in hypothalamus...
March 23, 2018: Neuroscience Research
https://www.readbyqxmd.com/read/29542425/progenitor-cell-proliferation-in-the-subventricular-zone-in-a-model-of-narcolepsy
#5
Oscar Arias-Carrion, Emmanuel Ortega-Robles, Benito de Celis-Alonso, Artur Palasz, Eric Murillo-Rodriguez, Miguel A Mendez-Rojas, Jose Salas-Pacheco, Elias Manjarrez
Adult neurogenesis, a specific form of brain plasticity in mammals occurring in the subventricular zone, is subject to complex regulations. Hypocretin/orexin neurons are implicated in the regulation of sleep and arousal states among other functions. Here, we found orexin afferent projections in the rat subventricular zone, which is a neurogenic region. We therefore studied in detail the origin of the orexinergic innervation to the subventricular zone in rats. Post-mortem retrograde tracing combined with immunofluorescence procedures indicate orexinergic projections toward the subventricular zone...
March 13, 2018: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/29541053/non-rapid-eye-movement-sleep-parasomnias-and-migraine-a-role-of-orexinergic-projections
#6
Antonietta Messina, Ilaria Bitetti, Francesco Precenzano, Diego Iacono, Giovanni Messina, Michele Roccella, Lucia Parisi, Margherita Salerno, Anna Valenzano, Agata Maltese, Monica Salerno, Francesco Sessa, Giuseppe Davide Albano, Rosa Marotta, Ines Villano, Gabriella Marsala, Christian Zammit, Francesco Lavano, Marcellino Monda, Giuseppe Cibelli, Serena Marianna Lavano, Beatrice Gallai, Roberto Toraldo, Vincenzo Monda, Marco Carotenuto
Introduction: Sleep and migraine share a common pathophysiological substrate, although the underlying mechanisms are unknown. The serotonergic and orexinergic systems are both involved in the regulation of sleep/wake cycle, and numerous studies show that both are involved in the migraine etiopathogenesis. These two systems are anatomically and functionally interconnected. Our hypothesis is that in migraine a dysfunction of orexinergic projections on the median raphe (MR) nuclei, interfering with serotonergic regulation, may cause Non-Rapid Eye Movement parasomnias, such as somnambulism...
2018: Frontiers in Neurology
https://www.readbyqxmd.com/read/29535612/neural-damage-in-experimental-trypanosoma-brucei-gambiense-infection-hypothalamic-peptidergic-sleep-and-wake-regulatory-neurons
#7
Claudia Laperchia, Yuan-Zhong Xu, Dieudonné Mumba Ngoyi, Tiziana Cotrufo, Marina Bentivoglio
Neuron populations of the lateral hypothalamus which synthesize the orexin (OX)/hypocretin or melanin-concentrating hormone (MCH) peptides play crucial, reciprocal roles in regulating wake stability and sleep. The disease human African trypanosomiasis (HAT), also called sleeping sickness, caused by extracellular Trypanosoma brucei ( T. b .) parasites, leads to characteristic sleep-wake cycle disruption and narcoleptic-like alterations of the sleep structure. Previous studies have revealed damage of OX and MCH neurons during systemic infection of laboratory rodents with the non-human pathogenic T...
2018: Frontiers in Neuroanatomy
https://www.readbyqxmd.com/read/29531056/dec2-modulates-orexin-expression-and-regulates-sleep
#8
Arisa Hirano, Pei-Ken Hsu, Luoying Zhang, Lijuan Xing, Thomas McMahon, Maya Yamazaki, Louis J Ptáček, Ying-Hui Fu
Adequate sleep is essential for physical and mental health. We previously identified a missense mutation in the human DEC2 gene ( BHLHE41 ) leading to the familial natural short sleep behavioral trait. DEC2 is a transcription factor regulating the circadian clock in mammals, although its role in sleep regulation has been unclear. Here we report that prepro-orexin , also known as hypocretin ( Hcrt ), gene expression is increased in the mouse model expressing the mutant h DEC2 transgene (h DEC2-P384R ). Prepro-orexin encodes a precursor protein of a neuropeptide producing orexin A and B (hcrt1 and hcrt2), which is enriched in the hypothalamus and regulates maintenance of arousal...
March 12, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29530376/a-comparative-study-of-methods-for-automatic-detection-of-rapid-eye-movement-abnormal-muscular-activity-in-narcolepsy
#9
Alexander Neergaard Olesen, Matteo Cesari, Julie Anja Engelhard Christensen, Helge Bjarup Dissing Sorensen, Emmanuel Mignot, Poul Jennum
OBJECTIVE: To evaluate rapid eye movement (REM) muscular activity in narcolepsy by applying five algorithms to electromyogram (EMG) recordings, and to investigate its value for narcolepsy diagnosis. PATIENTS/METHODS: A modified version of phasic EMG metric (mPEM), muscle activity index (MAI), REM atonia index (RAI), supra-threshold REM EMG activity metric (STREAM), and Frandsen method (FR) were calculated from polysomnography recordings of 20 healthy controls, 18 clinic controls (subjects suspected with narcolepsy but finally diagnosed without any sleep abnormality), 16 narcolepsy type one without REM sleep behavior disorder (RBD), nine narcolepsy type one with RBD, and 18 narcolepsy type two...
April 2018: Sleep Medicine
https://www.readbyqxmd.com/read/29530370/flow-cytometry-analysis-of-t-cell-subsets-in-cerebrospinal-fluid-of-narcolepsy-type-1-patients-with-long-lasting-disease
#10
Monica Moresco, Mariangela Lecciso, Darina Ocadlikova, Marco Filardi, Silvia Melzi, Birgitte Rahbek Kornum, Elena Antelmi, Fabio Pizza, Emmanuel Mignot, Antonio Curti, Giuseppe Plazzi
BACKGROUND: Type 1 narcolepsy (NT1) is a central hypersomnia linked to the destruction of hypocretin-producing neurons. A great body of genetic and epidemiological data points to likely autoimmune disease aetiology. Recent reports have characterized peripheral blood T-cell subsets in NT1, whereas data regarding the cerebrospinal fluid (CSF) immune cell composition are lacking. The current study aimed to characterize the T-cell and natural killer (NK) cell subsets in NT1 patients with long disease course...
April 2018: Sleep Medicine
https://www.readbyqxmd.com/read/29526023/contribution-of-dynorphin-and-orexin-neuropeptide-systems-to-the-motivational-effects-of-alcohol
#11
Rachel I Anderson, David E Moorman, Howard C Becker
Understanding the neural systems that drive alcohol motivation and are disrupted in alcohol use disorders is of critical importance in developing novel treatments. The dynorphin and orexin/hypocretin neuropeptide systems are particularly relevant with respect to alcohol use and misuse. Both systems are strongly associated with alcohol-seeking behaviors, particularly in cases of high levels of alcohol use as seen in dependence. Furthermore, both systems also play a role in stress and anxiety, indicating that disruption of these systems may underlie long-term homeostatic dysregulation seen in alcohol use disorders...
March 11, 2018: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/29522212/the-inappropriate-occurrence-of-rem-sleep-in-narcolepsy-is-not-due-to-a-defect-in-homeostatic-regulation-of-rem-sleep
#12
Alexis Roman, Soraya Meftah, Sébastien Arthaud, Pierre-Hervé Luppi, Christelle Peyron
Narcolepsy type 1 is a disabling disorder with four primary symptoms: excessive-daytime-sleepiness, cataplexy, hypnagogic hallucinations and sleep paralysis. The three latter symptoms together with a short REM sleep latency have suggested impairment in REM sleep homeostatic regulation with an enhanced propensity for (i.e. tendency to enter) REM sleep. To test this hypothesis, we challenged REM sleep homeostatic regulation in a recognized model of narcolepsy, the orexin knock-out (Orex-KO) mice and their wild-type (WT) littermates...
March 7, 2018: Sleep
https://www.readbyqxmd.com/read/29521652/nonpeptide-orexin-2-receptor-agonist-attenuates-morphine-induced-sedative-effects-in-rats
#13
Satoshi Toyama, Naohito Shimoyama, Yugo Tagaito, Hiroshi Nagase, Tsuyoshi Saitoh, Masashi Yanagisawa, Megumi Shimoyama
BACKGROUND: Sleepiness and decrease in attention are dose-limiting side effects of opioids. The orexin/hypocretin system plays an important role in maintaining wakefulness. This study aimed to explore the potential of a nonpeptide orexin receptor agonist to alleviate morphine-induced sedative effects. METHODS: Morphine sedative effects were evaluated as changes in electroencephalogram (EEG), locomotor activity, and acoustic startle response in rats (n = 5 to 9 per group)...
March 8, 2018: Anesthesiology
https://www.readbyqxmd.com/read/29512449/sodium-oxybate-treatment-in-pediatric-type-1-narcolepsy
#14
Monica Moresco, Fabio Pizza, Elena Antelmi, Giuseppe Plazzi
Narcolepsy type 1 (NT1) is a rare chronic neurologic disorder characterized by excessive daytime sleepiness, cataplexy, sleep paralysis, hallucinations and disrupted nocturnal sleep, usually with onset during childhood/adolescence. Pediatric NT1 is associated with limitations on children's activities and achievements, especially poor performance at school, difficulty with peers due to disease symptoms and comorbidities including depression, obesity, and precocious puberty. NT1 disease is caused by the selective loss of hypocretin-producing neurons in the lateral hypothalamus, most probably related to an autoimmune pathophysiology...
March 5, 2018: Current Drug Metabolism
https://www.readbyqxmd.com/read/29508004/the-hypocretin-orexin-system-as-a-target-for-excessive-motivation-in-alcohol-use-disorders
#15
REVIEW
David E Moorman
The hypocretin/orexin (ORX) system has been repeatedly demonstrated to regulate motivation for drugs of abuse, including alcohol. In particular, ORX seems to be critically involved in highly motivated behaviors, as is observed in high-seeking individuals in a population, in the seeking of highly palatable substances, and in models of dependence. It seems logical that this system could be considered as a potential target for treatment for addiction, particularly alcohol addiction, as ORX pharmacological manipulations significantly reduce drinking...
March 6, 2018: Psychopharmacology
https://www.readbyqxmd.com/read/29476336/neuroanatomical-and-neurochemical-bases-of-vigilance-states
#16
Pierre-Hervé Luppi, Patrice Fort
In the present chapter, hypotheses on the mechanisms responsible for the genesis of the three vigilance states, namely, waking, non-rapid eye movement (non-REM) also called slow-wave sleep (SWS), and REM sleep also called paradoxical sleep (PS), are presented. A huge number of studies first indicate that waking is induced by the activation of multiple waking systems, including the serotonergic, noradrenergic, cholinergic, and hypocretin systems. At the onset of sleep, the SWS-active neurons would be activated by the circadian clock localized in the suprachiasmatic nucleus and a hypnogenic factor, adenosine, which progressively accumulates in the brain during waking...
February 24, 2018: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/29471000/relationship-between-cerebrospinal-fluid-concentrations-of-orexin-a-hypocretin-1-and-body-composition-in-humans
#17
João C P Santiago, Markus Otto, Werner Kern, Paul Christian Baier, Manfred Hallschmid
The hypothalamic neuropeptide orexin A (hypocretin-1) is a key signal in sleep/wake regulation and promotes food intake. We investigated the relationship between cerebrospinal fluid orexin A concentrations and body composition in non-narcoleptic human subjects with a wide range of body weight to gain insight into the role of orexin A in human metabolism. We collected cerebrospinal fluid and blood samples and measured body composition by bioelectric impedance analysis in 36 subjects (16 women and 20 men) with body mass indices between 16...
February 19, 2018: Peptides
https://www.readbyqxmd.com/read/29467942/-in-vitro-in-vivo-and-ex-vivo-demonstration-of-the-antitumoral-role-of-hypocretin-1-orexin-a-and-almorexant-in-pancreatic-ductal-adenocarcinoma
#18
Stéphanie Dayot, Daniela Speisky, Anne Couvelard, Pierre Bourgoin, Valérie Gratio, Jérôme Cros, Vinciane Rebours, Alain Sauvanet, Pierre Bedossa, Valérie Paradis, Philippe Ruszniewski, Alain Couvineau, Thierry Voisin
Pancreatic ductal adenocarcinoma (PDAC) is still the poorest prognostic tumor of the digestive system. We investigated the antitumoral role of orexin-A and almorexant in PDAC. We analyzed the orexin receptor type 1 (OX1R) expression by immunohistochemistry in human normal pancreas, PDAC and its precursor dysplastic intraepithelial lesions. We used PDAC-derived cell lines and fresh tissue slices to study the apoptotic role of hypocretin-1/orexin-A and almorexant in vitro and ex vivo . We analyzed in vivo the hypocretin-1/orexin-A and almorexant effect on tumor growth in mice xenografted with PDAC cell lines expressing, or not, OX1R...
January 23, 2018: Oncotarget
https://www.readbyqxmd.com/read/29462275/excitation-of-cortical-nnos-nk1r-neurons-by-hypocretin-1-is-independent-of-sleep-homeostasis
#19
Rhîannan H Williams, Sarah W Black, Alexia M Thomas, Juliette Piquet, Bruno Cauli, Thomas S Kilduff
We have proposed that cortical nNOS/NK1R interneurons have a role in sleep homeostasis. The hypocretins (orexins) are wake-promoting neuropeptides and hypocretin/orexin (Hcrt) neurons project to the cortex. Hcrt peptides affect deep layer cortical neurons, and Hcrt receptor 1 (Hcrtr1; Ox1r) mRNA is expressed in cortical nNOS/NK1R cells. Therefore, we investigated whether Hcrt neuron stimulation affects cingulate cortex nNOS/NK1R neurons. Bath application of HCRT1/orexin-A evoked an inward current and membrane depolarization in most nNOS/NK1R cells which persisted in tetrodotoxin; optogenetic stimulation of Hcrt terminals expressing channelrhodopsin-2 confirmed these results, and pharmacological studies determined that HCRTR1 mediated these responses...
February 16, 2018: Cerebral Cortex
https://www.readbyqxmd.com/read/29454841/hypocretin-orexin-deficiency-decreases-cocaine-abuse-liability
#20
Nadia Steiner, Clara Rossetti, Takeshi Sakurai, Masashi Yanagisawa, Luis de Lecea, Pierre J Magistretti, Olivier Halfon, Benjamin Boutrel
Compelling evidence indicates that hypocretin/orexin signaling regulates arousal, stress and reward-seeking behaviors. However, most studies on drug reward-related processes have so far described the effects of pharmacological blockers disrupting hypocretin/orexin transmission. We report here an extensive study on cocaine-related behaviors in hypocretin/orexin-deficient mice (KO) and their heterozygous (HET) and wildtype (WT) littermates. We evaluated behavioral sensitization following repeated administrations and preference for an environment repeatedly paired with cocaine injections (15 mg/kg)...
February 15, 2018: Neuropharmacology
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