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https://www.readbyqxmd.com/read/28427008/lateral-hypothalamic-circuits-for-sleep-wake-control
#1
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/28424564/new-developments-in-the-management-of-narcolepsy
#2
REVIEW
Vivien C Abad, Christian Guilleminault
Narcolepsy is a life-long, underrecognized sleep disorder that affects 0.02%-0.18% of the US and Western European populations. Genetic predisposition is suspected because of narcolepsy's strong association with HLA DQB1*06-02, and genome-wide association studies have identified polymorphisms in T-cell receptor loci. Narcolepsy pathophysiology is linked to loss of signaling by hypocretin-producing neurons; an autoimmune etiology possibly triggered by some environmental agent may precipitate hypocretin neuronal loss...
2017: Nature and Science of Sleep
https://www.readbyqxmd.com/read/28419646/suvorexant-an-orexin-hypocretin-receptor-antagonist-attenuates-motivational-and-hedonic-properties-of-cocaine
#3
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/28414966/modeling-sleep-and-neuropsychiatric-disorders-in-zebrafish
#4
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
#5
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/28377228/sexually-dimorphic-changes-of-hypocretin-orexin-in-depression
#6
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/28366327/underutilization-of-the-mslt-in-sleepy-patients-with-a-short-onset-rem-period-soremp-in-the-sleep-clinic
#7
Alyssa Cairns, Richard Bogan
OBJECTIVE/BACKGROUND: A nocturnal sleep onset REM period (defined as REM onset latency ≤ 15 min; SOREMP) occurs rarely and research has shown that the phenomenon is specific for type 1 and 2 narcolepsy. However, little is known about the meaningfulness of the phenotype in general sleep clinic patients because those that exhibit the phenomenon often present with few traditional narcolepsy symptoms. As such, this study aimed to (1) evaluate the rate of eventual MSLT testing for those with a SOREMP on routine PSG when the phenomenon occurred in the absence of potential explanatory factors and (2) quantify the stability of the SOREMP phenotype...
April 2017: Sleep Medicine
https://www.readbyqxmd.com/read/28364500/antibodies-against-hypocretin-receptor-2-are-rare-in-narcolepsy
#8
Maria Pia Giannoccaro, Patrick Waters, Fabio Pizza, Rocco Liguori, Giuseppe Plazzi, Angela Vincent
Study Objectives: Recently, antibodies to the hypocretin receptor 2 (HCRTR2-Abs) were reported in a high proportion of narcolepsy patients who developed the disease following Pandemrix® vaccination. We tested a group of narcolepsy patients for the HCRTR2-Abs using a newly established cell-based assay. Methods: Sera from 50 narcolepsy type 1 (NT1) and 11 narcolepsy type 2 (NT2) patients, 22 patients with other sleep disorders, 15 healthy controls, and 93 disease controls were studied...
February 1, 2017: Sleep
https://www.readbyqxmd.com/read/28364477/temporal-changes-in-the-cerebrospinal-fluid-level-of-hypocretin-1-and-histamine-in-narcolepsy
#9
Régis Lopez, Lucie Barateau, Elisa Evangelista, Sofiene Chenini, Philippe Robert, Isabelle Jaussent, Yves Dauvilliers
Study Objectives: To follow the temporal changes of cerebrospinal fluid (CSF) biomarker levels in narcoleptic patients with unexpected hypocretin level at referral. Methods: From 2007 to 2015, 170 human leukocyte antigen (HLA) DQB1*06:02-positive patients with primary narcolepsy and definite (n = 155, 95 males, 60 females, 36 children) or atypical cataplexy (n = 15, 4 males, 3 children) were referred to our center. Cerebrospinal hypocretin deficiency was found in 95...
January 1, 2017: Sleep
https://www.readbyqxmd.com/read/28364459/anti-tribbles-pseudokinase-2-trib2-immunization-modulates-hypocretin-orexin-neuronal-functions
#10
Susumu Tanaka, Yoshiko Honda, Makoto Honda, Hisao Yamada, Kazuki Honda, Tohru Kodama
Study Objectives: Recent findings showed that 16%-26% of narcolepsy patients were positive for anti-tribbles pseudokinase 2 (TRIB2) antibody, and the intracerebroventricular administration of immunoglobulin-G purified from anti-TRIB2 positive narcolepsy patients caused hypocretin/orexin neuron loss. We investigated the pathophysiological role of TRIB2 antibody using TRIB2-immunized rats and hypocretin/ataxin-3 transgenic (ataxin-3) mice. Methods: Plasma, cerebrospinal fluid (CSF), and hypothalamic tissues from TRIB2-immunized rats were collected...
January 1, 2017: Sleep
https://www.readbyqxmd.com/read/28364448/cerebrospinal-fluid-biomarkers-of-neurodegeneration-are-decreased-or-normal-in-narcolepsy
#11
Poul Jørgen Jennum, Lars Østergaard Pedersen, Justyna Maria Czarna Bahl, Signe Modvig, Karina Fog, Anja Holm, Birgitte Rahbek Kornum, Steen Gammeltoft
Objectives: To investigate whether cerebrospinal fluid (CSF) biomarkers of neurodegeneration are altered in narcolepsy in order to evaluate whether the hypocretin deficiency and abnormal sleep-wake pattern in narcolepsy leads to neurodegeneration. Methods: Twenty-one patients with central hypersomnia (10 type 1 narcolepsy, 5 type 2 narcolepsy, and 6 idiopathic hypersomnia cases), aged 33 years on average and with a disease duration of 2-29 years, and 12 healthy controls underwent CSF analyses of the levels of β-amyloid, total tau protein (T-tau), phosphorylated tau protein (P-tau181), α-synuclein, neurofilament light chain (NF-L), and chitinase 3-like protein-1 (CHI3L1)...
January 1, 2017: Sleep
https://www.readbyqxmd.com/read/28364420/cd4-t-cell-reactivity-to-orexin-hypocretin-in-patients-with-narcolepsy-type-1
#12
Melanie Ramberger, Birgit Högl, Ambra Stefani, Thomas Mitterling, Markus Reindl, Andreas Lutterotti
Introduction: Narcolepsy type 1 is accompanied by a selective loss of orexin/hypocretin (hcrt) neurons in the lateral hypothalamus caused by yet unknown mechanisms. Epidemiologic and genetic associations strongly suggest an immune-mediated pathogenesis of the disease. Methods: We compared specific T-cell reactivity to orexin/hcrt peptides in peripheral blood mononuclear cells of narcolepsy type 1 patients to healthy controls by a carboxyfluorescein succinimidyl ester proliferation assay...
March 1, 2017: Sleep
https://www.readbyqxmd.com/read/28363787/comparative-analysis-of-biological-effect-of-corannulene-and-graphene-on-developmental-and-sleep-wake-profile-of-zebrafish-larvae
#13
Xiang Li, Yuan Zhang, Xu Li, DaoFu Feng, ShuHui Zhang, Xin Zhao, DongYan Chen, ZhiXiang Zhang, XiZeng Feng
Little is known about the biological effect of non-planar polycyclic aromatic hydrocarbons (PAH) such as corannulene on organisms. In this study, we compared the effect of corannulene (non-planar PAH) and graphene (planar PAH) on embryonic development and sleep/wake behaviors of larval zebrafish. First, the toxicity of graded doses of corannulene (1, 10, and 50 μg/mL) was tested in developing zebrafish embryos. Corannulene showed minimal developmental toxicity only induced an epiboly delay. Further, a significant decrease in locomotion/increase in sleep was observed in larvae treated with the highest dose (50 μg/mL) of corannulene while no significant locomotion alterations were induced by graphene...
March 28, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28353077/role-of-orexin-a-in-hypertension-and-obesity
#14
REVIEW
Imperatore Roberta, Palomba Letizia, Cristino Luigia
PURPOSE OF REVIEW: Hypertension is one of the most challenging health problems inducing cerebrovascular disease and high percentage of death when associated with diabetes, dyslipidemias, and obesity. Orexin/hypocretin is a peptide expressed by a small number of neurons of the dorsolateral hypothalamus, a brain feeding and autonomic "fight-or-flight" regulatory center. According to this function, orexin has been demonstrated to evoke cardiovascular responses, heart rate, hypertension, hyperarousal, hyperphagia, and obesity...
April 2017: Current Hypertension Reports
https://www.readbyqxmd.com/read/28344067/upregulation-of-orexin-hypocretin-expression-in-aged-rats-effects-on-feeding-latency-and-neurotransmission-in-the-insular-cortex
#15
Janel M Hagar, Victoria A Macht, Steven P Wilson, James R Fadel
Aging is associated with changes in numerous homeostatic functions, such as food intake, that are thought to be mediated by the hypothalamus. Orexin/hypocretin neurons of the hypothalamus regulate several physiological functions, including feeding, sleep and wakefulness. Evidence from both clinical and animal studies supports the notion that aging is associated with loss or dysregulation of the orexin system. Here, we used virus-mediated gene transfer to manipulate expression of orexin peptides in young and aged rats and examined behavioral and neurochemical correlates of food intake in these animals...
March 24, 2017: Neuroscience
https://www.readbyqxmd.com/read/28323938/loss-of-action-via-neurotensin-leptin-receptor-neurons-disrupts-leptin-and-ghrelin-mediated-control-of-energy-balance
#16
Juliette A Brown, Raluca Bugescu, Thomas Mayer, Adriana Gata-Garcia, Gizem Kurt, Hillary L Woodworth, Gina M Leinninger
The hormones ghrelin and leptin act via the lateral hypothalamic area (LHA) to modify energy balance but the underlying neural mechanisms remain unclear. We investigated how leptin and ghrelin engage LHA neurons to modify energy balance behaviors and whether there is any cross-talk between leptin and ghrelin-responsive circuits. We demonstrate that ghrelin activates LHA neurons expressing Hypocretin/Orexin (OX) to increase food intake. Leptin mediates anorectic actions via separate neurons expressing the long form of the leptin receptor (LepRb), many of which co-express the neuropeptide neurotensin (Nts); we refer to these as NtsLepRb neurons...
March 10, 2017: Endocrinology
https://www.readbyqxmd.com/read/28303403/hypocretin-orexin-and-plastic-adaptations-associated-with-drug-abuse
#17
Corey Baimel, Stephanie L Borgland
Dopamine neurons in the ventral tegmental area (VTA) are a critical part of the neural circuits that underlie reward learning and motivation. Dopamine neurons send dense projections throughout the brain and recent observations suggest that both the intrinsic properties and the functional output of dopamine neurons are dependent on projection target and are subject to neuromodulatory influences. Lateral hypothalamic hypocretin (also termed orexin) neurons project to the VTA and contain both hypocretin and dynorphin peptides in the same dense core vesicles suggesting they may be co-released...
March 17, 2017: Current Topics in Behavioral Neurosciences
https://www.readbyqxmd.com/read/28296947/the-dual-orexin-receptor-antagonist-tcs1102-does-not-affect-reinstatement-of-nicotine-seeking
#18
Shaun Yon-Seng Khoo, Gavan P McNally, Kelly J Clemens
The orexin/hypocretin system is important for appetitive motivation towards multiple drugs of abuse, including nicotine. Both OX1 and OX2 receptors individually have been shown to influence nicotine self-administration and reinstatement. Due to the increasing clinical use of dual orexin receptor antagonists in the treatment of disorders such as insomnia, we examined whether a dual orexin receptor antagonist may also be effective in reducing nicotine seeking. We tested the effect of intracerebroventricular (i...
2017: PloS One
https://www.readbyqxmd.com/read/28283054/orexin-hypocretin-central-amygdala-and-escalation-of-cocaine-intake
#19
Morgan H James, Gary Aston-Jones
No abstract text is available yet for this article.
April 1, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/28275716/genetic-analysis-of-histamine-signaling-in-larval-zebrafish-sleep
#20
Audrey Chen, Chanpreet Singh, Grigorios Oikonomou, David A Prober
Pharmacological studies in mammals and zebrafish suggest that histamine plays an important role in promoting arousal. However, genetic studies using rodents with disrupted histamine synthesis or signaling have revealed only subtle or no sleep/wake phenotypes. Studies of histamine function in mammalian arousal are complicated by its production in cells of the immune system and its roles in humoral and cellular immunity, which can have profound effects on sleep/wake states. To avoid this potential confound, we used genetics to explore the role of histamine in regulating sleep in zebrafish, a diurnal vertebrate in which histamine production is restricted to neurons in the brain...
January 2017: ENeuro
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