keyword
MENU ▼
Read by QxMD icon Read
search

Orexin

keyword
https://www.readbyqxmd.com/read/28631980/orexin-research-patent-news-from-2016
#1
Christoph Boss, Catherine Roch
The orexin (hypocretin) system consists of two G-protein-coupled receptors, orexin 1 (Ox1) and orexin 2 (Ox2) and two endogenous peptidic ligands, orexin A (OxA) and orexin B (OxB). It is evolutionarily highly conserved. In the brain, it is involved in the promotion of wakefulness under motivational circumstances as well as in anxiety and addictive disorders. In addition, its activation via the Ox1 receptor triggers apoptosis in several cancer cell lines. Dual orexin receptor antagonists (DORAs) such as suvorexant are successfully used to treat primary insomnia...
June 20, 2017: Expert Opinion on Therapeutic Patents
https://www.readbyqxmd.com/read/28630298/hypocretin-orexin-is-critical-in-sustaining-theta-gamma-rich-waking-behaviors-that-drive-sleep-need
#2
Anne Vassalli, Paul Franken
Hcrt gene inactivation in mice leads to behavioral state instability, abnormal transitions to paradoxical sleep, and cataplexy, hallmarks of narcolepsy. Sleep homeostasis is, however, considered unimpaired in patients and narcoleptic mice. We find that whereas Hcrt(ko/ko) mice respond to 6-h sleep deprivation (SD) with a slow-wave sleep (SWS) EEG δ (1.0 to 4.0 Hz) power rebound like WT littermates, spontaneous waking fails to induce a δ power reflecting prior waking duration. This correlates with impaired θ (6...
June 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28624370/leptin-orexin-peptide-yy-and-ghrelin-associated-with-relapse-during-smoking-cessation
#3
José Ignacio de Granda-Orive, Ana María de Granda-Beltrán, Gonzalo Segrelles-Calvo
No abstract text is available yet for this article.
June 14, 2017: Archivos de Bronconeumología
https://www.readbyqxmd.com/read/28620314/orexin-system-the-key-for-a-healthy-life
#4
REVIEW
Sergio Chieffi, Marco Carotenuto, Vincenzo Monda, Anna Valenzano, Ines Villano, Francesco Precenzano, Domenico Tafuri, Monica Salerno, Nicola Filippi, Francesco Nuccio, Maria Ruberto, Vincenzo De Luca, Luigi Cipolloni, Giuseppe Cibelli, Maria P Mollica, Diego Iacono, Ersilia Nigro, Marcellino Monda, Giovanni Messina, Antonietta Messina
The orexin-A/hypocretin-1 and orexin-B/hypocretin-2 are neuropeptides synthesized by a cluster of neurons in the lateral hypothalamus and perifornical area. Orexin neurons receive a variety of signals related to environmental, physiological and emotional stimuli, and project broadly to the entire CNS. Orexin neurons are "multi-tasking" neurons regulating a set of vital body functions, including sleep/wake states, feeding behavior, energy homeostasis, reward systems, cognition and mood. Furthermore, a dysfunction of orexinergic system may underlie different pathological conditions...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28608460/anatomical-and-electrophysiological-development-of-the-hypothalamic-orexin-neurons-from-embryos-to-neonates
#5
Yukino Ogawa, Takeshi Kanda, Kaspar Vogt, Masashi Yanagisawa
The amount, quality and diurnal pattern of sleep change greatly during development. Developmental changes of sleep/wake architecture are in a close relationship to brain development. The fragmentation of wake episodes is one of the salient features in the neonatal period, which is also observed in mature animals and human individuals lacking neuropeptide orexin/hypocretin signaling. This raises the possibility that developmental changes of lateral hypothalamic orexin neurons are relevant to the development of sleep/wake architecture...
June 12, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28601291/absence-of-autoreactive-cd4-t-cells-targeting-hla-dqa1-01-02-dqb1-06-02-restricted-hypocretin-orexin-epitopes-in-narcolepsy-type-1-when-detected-by-elispot
#6
Birgitte Rahbek Kornum, Kristoffer Sølvsten Burgdorf, Anja Holm, Henrik Ullum, Poul Jennum, Stine Knudsen
Narcolepsy type 1, a neurological sleep disorder strongly associated with Human Leukocyte Antigen (HLA-)DQB1*06:02, is caused by the loss of hypothalamic neurons producing the wake-promoting neuropeptide hypocretin (hcrt, also known as orexin). This loss is believed to be caused by an autoimmune reaction. To test whether hcrt itself could be a possible target in the autoimmune attack, CD4(+) T-cell reactivity towards six different 15-mer peptides from prepro-hypocretin with high predicted affinity to the DQA1*01:02/DQB1*06:02 MHC class II dimer was tested using EliSpot in a cohort of 22 narcolepsy patients with low CSF hcrt levels, and 23 DQB1*06:02 positive healthy controls...
August 15, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28594375/a-high-protein-diet-reduces-weight-gain-decreases-food-intake-decreases-liver-fat-deposition-and-improves-markers-of-muscle-metabolism-in-obese-zucker-rats
#7
William W French, Sami Dridi, Stephanie A Shouse, Hexirui Wu, Aubree Hawley, Sun-Ok Lee, Xuan Gu, Jamie I Baum
A primary factor in controlling and preventing obesity is through dietary manipulation. Diets higher in protein have been shown to improve body composition and metabolic health during weight loss. The objective of this study was to examine the effects of a high-protein diet versus a moderate-protein diet on muscle, liver and fat metabolism and glucose regulation using the obese Zucker rat. Twelve-week old, male, Zucker (fa/fa) and lean control (Fa/fa) rats were randomly assigned to either a high-protein (40% energy) or moderate-protein (20% energy) diet for 12 weeks, with a total of four groups: lean 20% protein (L20; n = 8), lean 40% protein (L40; n = 10), obese 20% protein (O20; n = 8), and obese 40% protein (O40; n = 10)...
June 8, 2017: Nutrients
https://www.readbyqxmd.com/read/28588546/neuroprotective-effects-of-physical-activity-evidence-from-human-and-animal-studies
#8
REVIEW
Sergio Chieffi, Giovanni Messina, Ines Villano, Antonietta Messina, Anna Valenzano, Fiorenzo Moscatelli, Monica Salerno, Alessio Sullo, Roberto Avola, Vincenzo Monda, Giuseppe Cibelli, Marcellino Monda
In the present article, we provide a review of current knowledge regarding the role played by physical activity (PA) in preventing age-related cognitive decline and reducing risk of dementia. The cognitive benefits of PA are highlighted by epidemiological, neuroimaging and behavioral studies. Epidemiological studies identified PA as an influential lifestyle factor in predicting rates of cognitive decline. Individuals physically active from midlife show a reduced later risk of cognitive impairment. Neuroimaging studies documented attenuation of age-related brain atrophy, and also increase of gray matter and white matter of brain areas, including frontal and temporal lobes...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28584695/neuroendocrine-autonomic-and-metabolic-responses-to-an-orexin-antagonist-suvorexant-in-psychiatric-patients-with-insomnia
#9
Masaru Nakamura, Takahiko Nagamine
Aim: The aim of this study was to investigate the neuroendocrine, autonomic, and metabolic system responses to suvorexant in psychiatric subjects with insomnia. Design: This prospective study was conducted in Kusatsu Hospital in Hiroshima, Japan and included 40 psychiatric inpatients treated with suvorexant from December 2014 to April 2016. Methods: Questionnaire of Pittsburgh Sleep Quality Index (PSQI), Generalized Anxiety Disorder-7 (GAD-7), and Patient Health Questionnaire-9 (PHQ-9) scores were checked at baseline, Week 2, and Week 4, and fasting serum levels of prolactin, insulin, cortisol, noradrenaline, white blood cell count, and average pulse rate were measured at baseline and Week 4 and Week 8 after suvorexant initiation...
March 2017: Innovations in Clinical Neuroscience
https://www.readbyqxmd.com/read/28583577/antagonism-of-orexin-type-1-receptors-ox1rs-attenuates-naloxone-precipitated-morphine-withdrawal-syndrome-in-rat-dorsal-hippocampus
#10
Mehdi Hooshmandi, Narges Hosseinmardi, Mahyar Janahmadi, Fatemeh Khakpai, Kambiz Rohampour, Jafar Doostmohammadi
Herein the effect of hippocampal orexin type-1 receptors (OX1Rs) blockade on morphine withdrawal syndrome was studied. Animals were made dependent by subcutaneous (s.c.) administration of morphine sulfate (10mg/kg) at an interval of 12h for 9 consecutive days. Thereafter, on day 10, naloxone hydrochloride (1.5mg/kg, i.p.) was injected and the somatic signs of withdrawal syndrome were monitored during a 25-min period. Two groups of animals received bilateral microinjection of either SB-334867, a selective OX1Rs antagonist, (0...
July 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/28582570/phase-ii-proof-of-concept-trial-of-the-orexin-receptor-antagonist-filorexant-mk-6096-in-patients-with-major-depressive-disorder
#11
Kathryn M Connor, Paulette Ceesay, Jill Hutzlemann, Duane Snavely, Andrew D Krystal, Madhukar H Trivedi, Michael Thase, Christopher Lines, W Joseph Herring, David Michelson
Background: We evaluated the orexin receptor antagonist filorexant (MK-6096) for treatment augmentation in patients with major depressive disorder (MDD). Methods: Six-week, double-blind, placebo-controlled, parallel-group, Phase II, proof-of-concept study. Patients with MDD (partial responders to ongoing antidepressant therapy) were randomized 1:1 to once-daily oral filorexant 10mg or matching placebo. Results: Due to enrollment challenges the study was terminated early, resulting in insufficient statistical power to detect a pre-specified treatment difference; of 326 patients planned, 129 (40%) were randomized and 128 took treatment...
June 3, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28580289/endocannabinoid-dependent-disinhibition-of-orexinergic-neurons-electrophysiological-evidence-in-leptin-knockout-obese-mice
#12
Thorsten Michael Becker, Morgana Favero, Vincenzo Di Marzo, Luigia Cristino, Giuseppe Busetto
OBJECTIVES: In the ob/ob mouse model of obesity, chronic absence of leptin causes a significant increase of orexin (OX) production by hypothalamic neurons and excessive food intake. The altered OX level is linked to a dramatic increase of the inhibitory innervation of OX producing neurons (OX neurons) and the over expression of the endocannabinoid 2-arachidonoylglycerol (2-AG) by OX neurons of ob/ob mice. Little is known about the function of the excitatory synapses of OX neurons in ob/ob mice, and their modulation by 2-AG...
June 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28580231/hormones-and-neuropeptide-receptor-heteromers-in-the-ventral-tegmental-area-targets-for-the-treatment-of-loss-of-control-of-food-intake-and-substance-use-disorders
#13
REVIEW
Sergi Ferré
Hormones and neuropeptides represent biological correlates of internal homeostatic signals detected and integrated in the hypothalamus, which establishes a robust functional connection with the ventral tegmental area (VTA). The hypothalamus-VTA connection determines the ability of these signals to influence central dopaminergic neurotransmission and, therefore, their ability to increase responsiveness to their reward-associated stimuli and to establish appropriate associative learning. The hypothalamus also provides the main source of the multiple neuropeptides that are released in the VTA...
2017: Current Treatment Options in Psychiatry
https://www.readbyqxmd.com/read/28575023/orexin-receptor-agonist-yan-7874-is-a-weak-agonist-of-orexin-hypocretin-receptors-and-shows-orexin-receptor-independent-cytotoxicity
#14
Ainoleena Turku, Maiju K Rinne, Gustav Boije Af Gennäs, Henri Xhaard, Dan Lindholm, Jyrki P Kukkonen
Two promising lead structures of small molecular orexin receptor agonist have been reported, but without detailed analyses of the pharmacological properties. One of them, 1-(3,4-dichlorophenyl)-2-[2-imino-3-(4-methylbenzyl)-2,3-dihydro-1H-benzo[d]imidazol-1-yl]ethan-1-ol (Yan 7874), is commercially available, and we set out to analyze its properties. As test system we utilized human OX1 and OX2 orexin receptor-expressing Chinese hamster ovary (CHO) K1 cells as well as control CHO-K1 and neuro-2a neuroblastoma cells...
2017: PloS One
https://www.readbyqxmd.com/read/28570646/diurnal-fluctuation-in-the-number-of-hypocretin-orexin-and-histamine-producing-implication-for-understanding-and-treating-neuronal-loss
#15
Ronald McGregor, Ling Shan, Ming-Fung Wu, Jerome M Siegel
The loss of specific neuronal phenotypes, as determined by immunohistochemistry, has become a powerful tool for identifying the nature and cause of neurological diseases. Here we show that the number of neurons identified and quantified using this method misses a substantial percentage of extant neurons in a phenotype specific manner. In mice, 24% more hypocretin/orexin (Hcrt) neurons are seen in the night compared to the day, and an additional 17% are seen after inhibiting microtubule polymerization with colchicine...
2017: PloS One
https://www.readbyqxmd.com/read/28559480/in-vitro-and-in-silico-characterization-of-lemborexant-e2006-a-novel-dual-orexin-receptor-antagonist
#16
Carsten Theodor Beuckmann, Michiyuki Suzuki, Takashi Ueno, Kazuya Nagaoka, Tohru Arai, Hiroyuki Higashiyama
Orexin (hypocretin) neuropeptides have, among others, been implicated in arousal/sleep control, and antagonizing the orexin signaling pathway has been previously demonstrated to promote sleep in animals and humans. This mechanism opens up a new therapeutic approach to curb excessive wakefulness in insomnia disorder, rather than to promote sleep-related signaling. Here we describe the preclinical pharmacological in vitro and in silico characterization of lemborexant (E2006: (1R,2S)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]methyl}-2-(3-fluorophenyl)-N-(5-fluoropyridin-2-yl)cyclopropanecarboxamide)), a dual orexin receptor antagonist (DORA), as a novel experimental therapeutic for the symptomatic treatment of insomnia disorder, and compare its properties to two other DORAs, almorexant and suvorexant...
May 30, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28552056/the-orexinergic-hypocretin-system-and-nociception-an-update-to-supraspinal-mechanisms
#17
Ali Roohbakhsh, Mohaddeseh Sadat Alavi, Hassan Azhdari Zarmehri
Chronic pain is a multifaceted and complex condition that is divided into somatic, visceral, and neuropathic pain. Although opioids and nonsteroidal anti-inflammatory drugs cause analgesia and are effective in the treatment of chronic pain, their utility is hampered by side effects, abuse potential, and development of tolerance to their pain-relieving effects. So, finding alternative analgesics with good efficacy and low side effects is of great interest and the orexinergic system is a potential candidate. Orexin-A and -B are exclusively expressed in the lateral hypothalamus and are involved in the feeding, sleep/wake cycle, cardiovascular function, hormone secretion, seizure, and pain modulation...
May 28, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28550253/is-sleep-disruption-a-risk-factor-for-alzheimer-s-disease
#18
Arthur Cassa Macedo, Sara Balouch, Naji Tabet
Sleep disturbances are routinely encountered in Alzheimer's disease (AD) and affect about 25-40% of patients in the mild-to-moderate stages of the disease. In many, sleep pathology may represent a symptom of the underlying neurodegeneration. However, a history of sleep disruption occurring years prior to onset of cognitive symptoms could represent a potential risk factor for AD. The aim of the present narrative review was to evaluate current evidence linking sleep disturbances with AD development and to understand the mechanisms that may contribute to this...
May 26, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28549933/orexin-exerts-excitatory-effects-on-reticulospinal-neurons-in-the-rat-gigantocellular-reticular-nucleus-through-the-activation-of-postsynaptic-orexin-1-and-orexin-2-receptors
#19
Nian Yang, Guan-Zhong Wang, Si-Yi Wen, Qi-Cheng Qiao, Yu-Hui Liu, Jun Zhang
Previous studies have revealed that orexin may actively participate in central motor control. The gigantocellular reticular nucleus (Gi) is a key element of the brainstem motor inhibitory system. The descending orexinergic projections also reach Gi region, and microinjection of orexin into Gi causes robust muscle tone inhibition. However, the modulation effects of orexin on Gi neurons remain unclear. In the present study, using whole-cell patch-clamp recordings, we initially observed that orexin elicited an inward current in Gi neurons at a holding potential of -70mV in a concentration-dependent manner...
May 24, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28549585/cystamine-mediated-inhibition-of-protein-disulfide-isomerase-triggers-aggregation-of-misfolded-orexin-a-in-the-golgi-apparatus-and-prevents-extracellular-secretion-of-orexin-a
#20
Issei Fujita, Mizuki Nobunaga, Takahiro Seki, Yuki Kurauchi, Akinori Hisatsune, Hiroshi Katsuki
Orexins (orexin-A and orexin-B) are neuropeptides that are reduced in narcolepsy, a sleep disorder that is characterized by excessive daytime sleepiness, sudden sleep attacks and cataplexy. However, it remains unclear how orexins in the brain and orexin neurons are reduced in narcolepsy. Orexin-A has two closely located intramolecular disulfide bonds and is prone to misfolding due to the formation of incorrect disulfide bonds. Protein disulfide isomerase (PDI) possesses disulfide interchange activity. PDI can modify misfolded orexin-A to its native form by rearrangement of two disulfide bonds...
May 23, 2017: Biochemical and Biophysical Research Communications
keyword
keyword
4153
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"