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https://www.readbyqxmd.com/read/28445807/rewiring-brain-circuits-to-block-cataplexy-in-murine-models-of-narcolepsy
#1
REVIEW
Meng Liu, Carlos Blanco-Centurion, Priyattam J Shiromani
Narcolepsy was first identified almost 130 years ago, but it was only 15 years ago that it was identified as a neurodegenerative disease linked to a loss of orexin neurons in the brain. It is unclear what causes the orexin neurons to die, but our strategy has been to place the gene for orexin into surrogate neurons in the validated mouse models of narcolepsy, and test whether it can block narcolepsy symptoms, such as cataplexy. In both the orexin knockout and the orexin-ataxin-3 mouse models of narcolepsy we have found that cataplexy can be blocked if the surrogate neurons are part of the circuit responsible for cataplexy...
April 23, 2017: Current Opinion in Neurobiology
https://www.readbyqxmd.com/read/28444767/the-dual-orexin-receptor-antagonist-dora-22-lowers-histamine-levels-in-the-lateral-hypothalamus-and-prefrontal-cortex-without-lowering-hippocampal-acetylcholine
#2
Lihang Leon Yao, Andres Ramirez, Anthony J Roecker, Steven Fox, Jason Uslaner, Sean M Smith, Robert Hodgson, Paul J Coleman, John J Renger, Christopher J Winrow, Anthony L Gotter
Chronic insomnia is defined as a persistent difficulty with sleep initiation maintenance or non-restorative sleep. The therapeutic standard of care for this condition is treatment with gamma-aminobutyric acid (GABA)A receptor modulators, which promote sleep but are associated with a panoply of side effects, including cognitive and memory impairment. Dual orexin receptor antagonists (DORAs) have recently emerged as an alternative therapeutic approach that acts via a distinct and more selective wake-attenuating mechanism with the potential to be associated with milder side effects...
April 26, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28442349/perinatal-programming-of-the-orexinergic-hypocretinergic-system-in-hypothalamus-and-anterior-pituitary-by-testosterone
#3
Natalia I Cataldi, Victoria A Lux-Lantos, Carlos Libertun
Orexins A/B derived from hypothalamic prepro-orexin (PPO) are agonists for orexin receptors 1 (OX1) and 2 (OX2). Previously, we showed clear sex differences in the hypothalamic-pituitary-gonadal orexinergic system in adult rodents. Here, we studied the effect of sexual brain differentiation on the orexinergic system in neuroendocrine structures regulating reproduction. We evaluated: a: proestrous and neonatally androgenized female rats; b: adult males, untreated or gonadectomized in adulthood and injected with oil or estradiol and progesterone (E2/P4); c: control and demasculinized males (perinatally treated with flutamide and later castration) injected either with oil or E2/P4 in adulthood...
April 22, 2017: Peptides
https://www.readbyqxmd.com/read/28427826/suvorexant-in-elderly-patients-with-insomnia-pooled-analyses-of-data-from-phase-iii-randomized-controlled-clinical-trials
#4
W Joseph Herring, Kathryn M Connor, Ellen Snyder, Duane B Snavely, Ying Zhang, Jill Hutzelmann, Deborah Matzura-Wolfe, Ruth M Benca, Andrew D Krystal, James K Walsh, Christopher Lines, Thomas Roth, David Michelson
OBJECTIVE: Suvorexant is an orexin receptor antagonist approved for treating insomnia at doses of 10-20 mg. Previously reported phase III results showed that suvorexant was effective and well-tolerated in a combined-age population (elderly and nonelderly adults). The present analysis evaluated the clinical profile of suvorexant specifically in the elderly. METHODS: Prespecified subgroup analyses of pooled 3-month data from two (efficacy) and three (safety) randomized, double-blind, placebo-controlled, parallel-group trials...
March 8, 2017: American Journal of Geriatric Psychiatry
https://www.readbyqxmd.com/read/28427008/lateral-hypothalamic-circuits-for-sleep-wake-control
#5
REVIEW
Takayuki Yamashita, Akihiro Yamanaka
The lateral hypothalamic area (LHA) of the diencephalon is crucially involved in controlling instinctive behavior such as sleep-wake cycle and feeding behavior. LHA is a heterogeneous structure that contains spatially intermingled, genetically distinct cell populations. Among LHA neurons, orexin/hypocretin (OX) neuron is the key cell type that promotes waking, and specific loss of OX neurons results in narcolepsy. Melanin-concentrating hormone (MCH) containing neurons are known to be active during rapid eye movement (REM) sleep and stimulation of these neurons promotes REM sleep...
April 17, 2017: Current Opinion in Neurobiology
https://www.readbyqxmd.com/read/28420957/neuropeptide-y-induced-orexigenic-action-is-attenuated-by-the-orexin-receptor-antagonist-in-bullfrog-larvae
#6
Kouhei Matsuda, Kairi Matsumura, Syun-Suke Shimizu, Tomoya Nakamachi, Norifumi Konno
In bullfrog larvae at the pre- and pro-metamorphic stages, feeding behavior is regulated by appetite factors such as orexigenic peptides. In fact, food intake is enhanced by intracerebroventricular (ICV) administration of neuropeptide Y (NPY) and orexin A. Using goldfish, our previous study indicated that the orexigenic action of NPY is mediated by orexin A, suggesting the functional interaction between the two. However, there is little information about whether the action of orexin A mediates the orexigenic action of NPY in bullfrog larvae...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28419646/suvorexant-an-orexin-hypocretin-receptor-antagonist-attenuates-motivational-and-hedonic-properties-of-cocaine
#7
Taylor A Gentile, Steven J Simmons, David J Barker, Jessica K Shaw, Rodrigo A España, John W Muschamp
Orexins ('hypocretins') are peptides produced by neurons of the hypothalamus that project to structures implicated in reward and emotion processing. Converging evidence demonstrates functional roles of orexin signaling in arousal, sleep/wakefulness and motivated behaviors for natural and drug rewards. Suvorexant, a dual orexin receptor antagonist, recently received approval from the US Food and Drug Administration to treat insomnia. In Experiment 1, rats self-administered cocaine under a progressive-ratio schedule of reinforcement and the effects of suvorexant on motivation to self-administer cocaine were measured...
April 17, 2017: Addiction Biology
https://www.readbyqxmd.com/read/28416460/regional-distribution-of-cholinergic-catecholaminergic-serotonergic-and-orexinergic-neurons-in-the-brain-of-two-carnivore-species-the-feliform-banded-mongoose-mungos-mungo-and-the-caniform-domestic-ferret-mustela-putorius-furo
#8
Sashrika Pillay, Adhil Bhagwandin, Mads F Bertelsen, Nina Patzke, Gerhard Engler, Andreas K Engel, Paul R Manger
The nuclear organization of the cholinergic, catecholaminergic, serotonergic and orexinergic neurons in the brains of two species of carnivore, the banded mongoose (Mungos mungo) and domestic ferret (Mustela putorius furo), is presented. The banded mongoose belongs to the feliform suborder and the domestic ferret to the caniform suborder, having last shared a common ancestor approximately 53 million years ago; however, they have a very similar overall morphology and life history, presenting an interesting opportunity to examine the extent of evolutionary plasticity in these systems...
April 14, 2017: Journal of Chemical Neuroanatomy
https://www.readbyqxmd.com/read/28414966/modeling-sleep-and-neuropsychiatric-disorders-in-zebrafish
#9
REVIEW
Talia Levitas-Djerbi, Lior Appelbaum
What are the molecular and cellular mechanisms that link neurological disorders and sleep disturbances? The transparent zebrafish model could bridge this gap in knowledge due to its unique genetic and imaging toolbox, and amenability to high-throughput screening. Sleep is well-characterized in zebrafish and key regulators of the sleep/wake cycle are conserved, including melatonin and hypocretin/orexin (Hcrt), whereas novel sleep regulating proteins are continually being identified, such as Kcnh4a, Neuromedin U, and QRFP...
April 14, 2017: Current Opinion in Neurobiology
https://www.readbyqxmd.com/read/28396432/serotonin-neurons-in-the-dorsal-raphe-mediate-the-anticataplectic-action-of-orexin-neurons-by-reducing-amygdala-activity
#10
Emi Hasegawa, Takashi Maejima, Takayuki Yoshida, Olivia A Masseck, Stefan Herlitze, Mitsuhiro Yoshioka, Takeshi Sakurai, Michihiro Mieda
Narcolepsy is a sleep disorder caused by the loss of orexin (hypocretin)-producing neurons and marked by excessive daytime sleepiness and a sudden weakening of muscle tone, or cataplexy, often triggered by strong emotions. In a mouse model for narcolepsy, we previously demonstrated that serotonin neurons of the dorsal raphe nucleus (DRN) mediate the suppression of cataplexy-like episodes (CLEs) by orexin neurons. Using an optogenetic tool, in this paper we show that the acute activation of DRN serotonin neuron terminals in the amygdala, but not in nuclei involved in regulating rapid eye-movement sleep and atonia, suppressed CLEs...
April 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28396414/orexin-driven-gad65-network-of-the-lateral-hypothalamus-sets-physical-activity-in-mice
#11
Christin Kosse, Cornelia Schöne, Edward Bracey, Denis Burdakov
Damage to the lateral hypothalamus (LH) causes profound physical inactivity in mammals. Several molecularly distinct types of LH neurons have been identified, including orexin cells and glutamic acid decarboxylase 65 (GAD65) cells, but their interplay in orchestrating physical activity is not fully understood. Here, using optogenetic circuit analysis and cell type-specific deep-brain recordings in behaving mice, we show that orexin cell activation rapidly recruits GAD65LH neurons. We demonstrate that internally initiated GAD65LH cell bursts precede and accompany spontaneous running bouts, that selective chemogenetic silencing of natural GAD65LH cell activity depresses voluntary locomotion, and that GAD65LH cell overactivation leads to hyperlocomotion...
April 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28392556/role-of-orexin-a-in-the-ventrolateral-preoptic-area-on-components-of-total-energy-expenditure
#12
J E Coborn, D P DePorter, V Mavanji, C M Sinton, C M Kotz, C J Billington, J A Teske
BACKGROUND: Identifying whether components of total EE are affected by orexin receptor (OXR1 and OXR2) stimulation or antagonism with dual orexin receptor antagonists (DORAs) has relevance for obesity treatment. Orexin receptor stimulation reduces weight gain by increasing total energy expenditure (EE) and EE during spontaneous physical activity (SPA). OBJECTIVE: The purpose of this study was to determine if a DORA (TCS-1102) in the ventrolateral preoptic area (VLPO) reduced orexin-A-induced arousal, SPA, total EE and EE during sleep, rest, wake and SPA and whether the DORA alone reduced total EE and its components...
April 10, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28389870/orexin-directly-enhances-the-excitability-of-globus-pallidus-internus-neurons-in-rat-by-co-activating-ox1-and-ox2-receptors
#13
He-Ren Gao, Qian-Xing Zhuang, Yong-Xiao Zhang, Zhang-Peng Chen, Bin Li, Xiao-Yang Zhang, Yi-Ting Zhong, Jian-Jun Wang, Jing-Ning Zhu
Orexin, released from the hypothalamus, has been implicated in various basic non-somatic functions including feeding, the sleep-wakefulness cycle, emotion, and cognition. However, the role of orexin in somatic motor control is still little known. Here, using whole-cell patch clamp recording and immunostaining, we investigated the effect and the underlying receptor mechanism of orexin-A on neurons in the globus pallidus internus (GPi), a critical structure in the basal ganglia and an effective target for deep brain stimulation therapy...
April 7, 2017: Neuroscience Bulletin
https://www.readbyqxmd.com/read/28387679/orexin-impairs-the-phagocytosis-and-degradation-of-amyloid-%C3%AE-fibrils-by-microglial-cells
#14
Hoyoung An, Mi-Hyang Cho, Dong-Hou Kim, Seockhoon Chung, Seung-Yong Yoon
BACKGROUND: Intracranial accumulation of amyloid-β (Aβ) is a characteristic finding of Alzheimer's disease (AD). It is thought to be the result of Aβ overproduction by neurons and impaired clearance by several systems, including degradation by microglia. Sleep disturbance is now considered a risk factor for AD, but studies focusing on how sleep modulates microglial handling of Aβ have been scarce. OBJECTIVE: To determine whether phagocytosis and degradation of extracellular Aβ fibrils by BV2 microglial cells were impaired by treatment with orexin-A/B, a major modulator of the sleep-wake cycle, which may mimic sleep deprivation conditions...
April 3, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28385341/enhancement-of-%C3%AE-opioid-receptor-desensitization-by-orexin-a-in-rat-locus-coeruleus-neurons
#15
S Mohammad Ahmadi Soleimani, Hossein Azizi, Narges Pachenari, Javad Mirnajafi-Zadeh, Saeed Semnanian
Opioids have always been used in clinical practice for pain management. However, development of tolerance to their effects following long term administration, seriously restricts further clinical use of these drugs. In this regard, μ-opioid receptor (MOR) desensitization, as an initial step in development of opioid tolerance, is of particular significance. Previous studies support the involvement of orexinergic system in development of opioid tolerance. Locus coeruleus (LC) nucleus has been shown to modulate pain and development of tolerance...
March 23, 2017: Neuropeptides
https://www.readbyqxmd.com/read/28380517/surface-wetting-strategy-prevents-acute-heat-exposure-induced-alterations-of-hypothalamic-stress-and-metabolic-related-genes-in-broiler-chickens
#16
H Rajaei-Sharifabadi, E Greene, A Piekarski, D Falcon, L Ellestad, A Donoghue, W Bottje, T Porter, Y Liang, S Dridi
Heat stress (HS) is devastating to poultry production worldwide, yet its biology and molecular responses are not well defined. Although advances in management strategy have partially alleviated the negative impact of HS, productivity still continues to decline when the ambient temperature rises. Therefore, identifying mechanism-based approaches to decrease HS susceptibility while improving production traits is critical. Recently, we made a breakthrough by applying a surface wetting strategy and showing that it improves growth performance compared with the current conventional cooling system...
March 2017: Journal of Animal Science
https://www.readbyqxmd.com/read/28377228/sexually-dimorphic-changes-of-hypocretin-orexin-in-depression
#17
Jing Lu, Juan Zhao, Rawien Balesar, Rolf Fronczek, Qiong-Bin Zhu, Xue-Yan Wu, Shao-Hua Hu, Ai-Min Bao, Dick F Swaab
BACKGROUND: Neurophysiological and behavioral processes regulated by hypocretin (orexin) are severely affected in depression. However, alterations in hypocretin have so far not been studied in the human brain. We explored the hypocretin system changes in the hypothalamus and cortex in depression from male and female subjects. METHODS: We quantified the differences between depression patients and well-matched controls, in terms of hypothalamic hypocretin-1 immunoreactivity (ir) and hypocretin receptors (Hcrtr-receptors)-mRNA in the anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex...
March 31, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28377124/characterization-of-appetite-regulating-factors-in-platyfish-xiphophorus-maculatus-cyprinodontiformes-poeciliidae
#18
Paul M Pitts, Hélène Volkoff
The regulation of energy in fish, like most vertebrates, is a complex process that involves a number of brain and peripheral hormones. These signals include anorexigenic (e.g. cholecystokinin (CCK) and cocaine- and amphetamine-regulated transcript (CART)) as well as orexigenic (e.g. orexin and neuropeptide Y (NPY)) peptides. Platyfish, Xiphophorus maculatus, are freshwater viviparous fish for which little is known about the endocrine mechanisms regulating feeding. In order to elucidate the role of these peptides in the regulation of feeding of platyfish, we examined the effects of peripheral injections of CCK and orexin on feeding behavior and food intake...
April 3, 2017: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
https://www.readbyqxmd.com/read/28376227/simple-and-highly-sensitive-uplc-esi-ms-ms-assay-for-rapid-determination-of-suvorexant-in-plasma
#19
Muzaffar Iqbal, Essam Ezzeldin, Nasr Y Khalil, Sara T A Al-Rashood, Khalid A Al-Rashood
Suvorexant is a dual orexin receptor antagonist, recently approved by USFDA for the treatment of insomnia. It is drug-of-abuse and listed in Schedule IV drug of the Controlled Substances Act. In this study, a simple and highly sensitive UPLC-MS/MS assay was developed and fully validated for the determination of suvorexant in rat plasma. Both suvorexant and internal standard (rivaroxaban; IS) were separated on Aquity BEHTM C18 column after the extraction form plasma using diethyl ether as extracting agent. An isocratic mobile phase, consisting of acetonitrile and 10 mM ammonium acetate in composition ratio of 85:15 was eluted at flow rate of 0...
March 1, 2017: Journal of Analytical Toxicology
https://www.readbyqxmd.com/read/28373831/interactions-of-circadian-rhythmicity-stress-and-orexigenic-neuropeptide-systems-implications-for-food-intake-control
#20
REVIEW
Anna Blasiak, Andrew L Gundlach, Grzegorz Hess, Marian H Lewandowski
Many physiological processes fluctuate throughout the day/night and daily fluctuations are observed in brain and peripheral levels of several hormones, neuropeptides and transmitters. In turn, mediators under the "control" of the "master biological clock" reciprocally influence its function. Dysregulation in the rhythmicity of hormone release as well as hormone receptor sensitivity and availability in different tissues, is a common risk-factor for multiple clinical conditions, including psychiatric and metabolic disorders...
2017: Frontiers in Neuroscience
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