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Hypocretin

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https://www.readbyqxmd.com/read/27909992/roles-for-orexin-hypocretin-in-the-control-of-energy-balance-and-metabolism
#1
Paulette B Goforth, Martin G Myers
The neuropeptide hypocretin is also commonly referred to as orexin, since its orexigenic action was recognized early. Orexin/hypocretin (OX) neurons project widely throughout the brain and the physiologic and behavioral functions of OX are much more complex than initially conceived based upon the stimulation of feeding. OX most notably controls functions relevant to attention, alertness, and motivation. OX also plays multiple crucial roles in the control of food intake, metabolism, and overall energy balance in mammals...
December 2, 2016: Current Topics in Behavioral Neurosciences
https://www.readbyqxmd.com/read/27909991/the-role-of-orexins-hypocretins-in-alcohol-use-and-abuse
#2
Leigh C Walker, Andrew J Lawrence
Addiction is a chronic relapsing disorder characterized by compulsive drug seeking and drug taking despite negative consequences. Alcohol abuse and addiction have major social and economic consequences and cause significant morbidity and mortality worldwide. Currently available therapeutics are inadequate, outlining the need for alternative treatments. Detailed knowledge of the neurocircuitry and brain chemistry responsible for aberrant behavior patterns should enable the development of novel pharmacotherapies to treat addiction...
December 2, 2016: Current Topics in Behavioral Neurosciences
https://www.readbyqxmd.com/read/27909990/orexin-hypocretin-signaling
#3
Jyrki P Kukkonen
Orexin/hypocretin peptide (orexin-A and orexin-B) signaling is believed to take place via the two G-protein-coupled receptors (GPCRs), named OX1 and OX2 orexin receptors, as described in the previous chapters. Signaling of orexin peptides has been investigated in diverse endogenously orexin receptor-expressing cells - mainly neurons but also other types of cells - and in recombinant cells expressing the receptors in a heterologous manner. Findings in the different systems are partially convergent but also indicate cellular background-specific signaling...
December 2, 2016: Current Topics in Behavioral Neurosciences
https://www.readbyqxmd.com/read/27865546/french-consensus-management-of-patients-with-hypersomnia-which-strategy
#4
R Lopez, I Arnulf, X Drouot, M Lecendreux, Y Dauvilliers
Central hypersomnias principally involves type 1 narcolepsy (NT1), type 2 narcolepsy (NT2) and idiopathic hypersomnia (IH). Despite great progress made in understanding the physiopathology of NT1 with low cerebrospinal fluid hypocretin-1 levels, current treatment remains symptomatic. The same applies to NT2 and IH, for which the physiopathology is still largely unknown. Controlling excessive daytime sleepiness (EDS), cataplexy, hypnagogic hallucinations, sleep paralysis and disturbed night-time sleep are key therapeutic targets in NT1...
November 16, 2016: Revue Neurologique
https://www.readbyqxmd.com/read/27855758/antibodies-against-hypocretin-receptor-2-are-rare-in-narcolepsy
#5
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 with type 2 (NT2), 22 patients with other sleep disorders, 15 healthy controls and 93 disease controls were studied...
November 14, 2016: Sleep
https://www.readbyqxmd.com/read/27855741/normal-morning-mch-levels-and-no-association-with-rem-or-nrem-sleep-parameters-in-narcolepsy-type-1-and-type-2
#6
Maren Schrölkamp, Poul J Jennum, Steen Gammeltoft, Anja Holm, Birgitte R Kornum, Stine Knudsen
STUDY OBJECTIVES: Other than hypocretin-1 (HCRT-1) deficiency in narcolepsy type 1 (NT1), the neurochemical imbalance of NT1 and narcolepsy type 2 (NT2) with normal HCRT-1 levels is largely unknown. The neuropeptide melanin-concentrating hormone (MCH) is mainly secreted during sleep and is involved in rapid eye movement (REM) and nonrapid eye movement (NREM) sleep regulation. Hypocretin neurons reciprocally interact with MCH neurons. We hypothesized that altered MCH secretion contributes to the symptoms and sleep abnormalities of narcolepsy and that this is reflected in morning cerebrospinal fluid (CSF) MCH levels, in contrast to previously reported normal evening/afternoon levels...
November 14, 2016: Journal of Clinical Sleep Medicine: JCSM: Official Publication of the American Academy of Sleep Medicine
https://www.readbyqxmd.com/read/27830577/orexin-hypocretin-and-organizing-principles-for-a-diversity-of-wake-promoting-neurons-in-the-brain
#7
Cornelia Schöne, Denis Burdakov
An enigmatic feature of behavioural state control is the rich diversity of wake-promoting neural systems. This diversity has been rationalized as 'robustness via redundancy', wherein wakefulness control is not critically dependent on one type of neuron or molecule. Studies of the brain orexin/hypocretin system challenge this view by demonstrating that wakefulness control fails upon loss of this neurotransmitter system. Since orexin neurons signal arousal need, and excite other wake-promoting neurons, their actions illuminate nonredundant principles of arousal control...
November 10, 2016: Current Topics in Behavioral Neurosciences
https://www.readbyqxmd.com/read/27824065/optogenetic-activation-of-serotonergic-terminals-facilitates-gabaergic-inhibitory-input-to-orexin-hypocretin-neurons
#8
Srikanta Chowdhury, Akihiro Yamanaka
Orexin/hypocretin neurons play a crucial role in the regulation of sleep/wakefulness, primarily in the maintenance of wakefulness. These neurons innervate wide areas of the brain and receive diverse synaptic inputs including those from serotonergic (5-HT) neurons in the raphe nucleus. Previously we showed that pharmacological application of 5-HT directly inhibited orexin neurons via 5-HT1A receptors. However, it was still unclear how 5-HT neurons regulated orexin neurons since 5-HT neurons contain not only 5-HT but also other neurotransmitters...
November 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27771284/orexin-hypocretin-1-receptor-antagonism-reduces-ethanol-self-administration-and-reinstatement-selectively-in-highly-motivated-rats
#9
David E Moorman, Morgan H James, Elisabeth A Kilroy, Gary Aston-Jones
The orexin/hypocretin (ORX) system regulates motivation for natural rewards and drugs of abuse such as alcohol. ORX receptor antagonists, most commonly OX1R antagonists including SB-334867 (SB), decrease alcohol drinking, self-administration and reinstatement in both genetically-bred alcohol-preferring and outbred strains of rats. Importantly, levels of alcohol seeking and drinking in outbred rats are variable, as they are in humans. We have shown that OX1R antagonism selectively decreases homecage alcohol drinking in high-, but not low-alcohol-preferring rats...
January 1, 2017: Brain Research
https://www.readbyqxmd.com/read/27746379/cellular-activation-of-hypothalamic-hypocretin-orexin-neurons-facilitates-short-term-spatial-memory-in-mice
#10
Teemu Aitta-Aho, Elpiniki Pappa, Denis Burdakov, John Apergis-Schoute
The hypothalamic hypocretin/orexin (HO) system holds a central role in the regulation of several physiological functions critical for food-seeking behavior including mnemonic processes for effective foraging behavior. It is unclear however whether physiological increases in HO neuronal activity can support such processes. Using a designer rM3Ds receptor activation approach increasing HO neuronal activity resulted in improved short-term memory for novel locations. When tested on a non-spatial novelty object recognition task no significant difference was detected between groups indicating that hypothalamic HO neuronal activation can selectively facilitate short-term spatial memory for potentially supporting memory for locations during active exploration...
December 2016: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/27746261/activation-of-orexin-hypocretin-neurons-is-associated-with-individual-differences-in-cued-fear-extinction
#11
Amanda C Sharko, Jim R Fadel, Kris F Kaigler, Marlene A Wilson
Identifying the neurobiological mechanisms that underlie differential sensitivity to stress is critical for understanding the development and expression of stress-induced disorders, such as post-traumatic stress disorder (PTSD). Preclinical studies have suggested that rodents display different phenotypes associated with extinction of Pavlovian conditioned fear responses, with some rodent populations being resistant to extinction. An emerging literature also suggests a role for orexins in the consolidation processes associated with fear learning and extinction...
October 13, 2016: Physiology & Behavior
https://www.readbyqxmd.com/read/27734337/sleep-dependent-structural-synaptic-plasticity-of-inhibitory-synapses-in-the-dendrites-of-hypocretin-orexin-neurons
#12
Idan Elbaz, David Zada, Adi Tovin, Tslil Braun, Tali Lerer-Goldshtein, Gordon Wang, Philippe Mourrain, Lior Appelbaum
Sleep is tightly regulated by the circadian clock and homeostatic mechanisms. Although the sleep/wake cycle is known to be associated with structural and physiological synaptic changes that benefit the brain, the function of sleep is still debated. The hypothalamic hypocretin/orexin (Hcrt) neurons regulate various functions including feeding, reward, sleep, and wake. Continuous imaging of single neuronal circuits in live animals is vital to understanding the role of sleep in regulating synaptic dynamics, and the transparency of the zebrafish model enables time-lapse imaging of single synapses during both day and night...
October 12, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27717810/activation-of-state-regulating-neurochemical-systems-in-newborn-and-embryonic-chicks
#13
Aimee Chan, SiHan Li, Ahn R Lee, Joseph Leung, Alissa Yip, Jaimie Bird, Kyle E Godden, Dolores Martinez-Gonzalez, Niels C Rattenborg, Evan Balaban, Maria Pompeiano
Coordinated activity in different sets of widely-projecting neurochemical systems characterize waking (W) and sleep (S). How and when this coordination is achieved during development is not known. We used embryos and newborns of a precocial bird species (chickens) to assess developmental activation in different neurochemical systems using cFos expression, which has been extensively employed to examine cellular activation during S and W in adult mammals. Similarly to adult mammals, newborn awake chicks showed significantly higher cFos expression in W-active hypocretin/orexin (H/O), serotonergic Dorsal Raphe, noradrenergic Locus Coeruleus and cholinergic Laterodorsal and Pedunculopontine Tegmental (Ch-LDT/PT) neurons when compared to sleeping chicks...
December 17, 2016: Neuroscience
https://www.readbyqxmd.com/read/27683906/hypocretin-orexin-peptides-alter-spike-encoding-by-serotonergic-dorsal-raphe-neurons-through-two-distinct-mechanisms-that-increase-the-late-afterhyperpolarization
#14
Masaru Ishibashi, Iryna Gumenchuk, Kenichi Miyazaki, Takafumi Inoue, William N Ross, Christopher S Leonard
UNLABELLED: Orexins (hypocretins) are neuropeptides that regulate multiple homeostatic processes, including reward and arousal, in part by exciting serotonergic dorsal raphe neurons, the major source of forebrain serotonin. Here, using mouse brain slices, we found that, instead of simply depolarizing these neurons, orexin-A altered the spike encoding process by increasing the postspike afterhyperpolarization (AHP) via two distinct mechanisms. This orexin-enhanced AHP (oeAHP) was mediated by both OX1 and OX2 receptors, required Ca(2+) influx, reversed near EK, and decayed with two components, the faster of which resulted from enhanced SK channel activation, whereas the slower component decayed like a slow AHP (sAHP), but was not blocked by UCL2077, an antagonist of sAHPs in some neurons...
September 28, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27676302/feeding-behavior-hypocretin-orexin-neurons-act-between-food-seeking-and-eating
#15
Xiao-Bing Gao, Tamas L Horvath
A report on the rapid change of activity of hypocretin/orexin cells in response to contact rather than digestion of food delivers new insights into the behavioral control of food intake and systemic energy expenditure.
September 26, 2016: Current Biology: CB
https://www.readbyqxmd.com/read/27641968/modulation-of-nociception-by-medial-pre-optic-area-orexin-a-receptors-and-its-relation-with-morphine-in-male-rats
#16
Amir Hossein Emam, Naeimeh Hajesfandiari, Siamak Shahidi, Alireza Komaki, Maziar Ganji, Abdolrahman Sarihi
INTRODUCTION: Recent studies have shown that medial pre-optic area (MPOA) of hypothalamus are involved in nociception. Orexin A (hypocretin 1) has been found to have numerous applications including pain modulation. However, the role of orexin A receptors in the MPOA on the nociception has not been yet studied. Therefore, the aim of the present study is to investigate the effect of orexin A microinjection on MPOA on the nociception transmission and morphine induced analgesia in adult male rats...
September 15, 2016: Brain Research Bulletin
https://www.readbyqxmd.com/read/27634798/anti-tribbles-pseudokinase-2-trib2-immunization-modulates-hypocretin-orexin-neuronal-functions
#17
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 IgG 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...
September 9, 2016: Sleep
https://www.readbyqxmd.com/read/27634795/temporal-changes-in-the-cerebrospinal-fluid-level-of-hypocretin-1-and-histamine-in-narcolepsy
#18
Régis Lopez, Lucie Barateau, Elisa Evangelista, Sofiene Chenini, Philippe Robert, Isabelle Jaussent, Yves Dauvilliers
STUDY OBJECTIVES: To follow the temporal changes of cerebrospinal fluid biomarker levels in narcoleptic patients with unexpected hypocretin level at referral. METHODS: From 2007 to 2015, 170 HLA DQB1*06:02-positive patients with primary narcolepsy and definite (n=155, 95 males, 36 children) or atypical cataplexy (n=15, 4 males, 3 children) were referred to our center. Cerebrospinal hypocretin deficiency was found in 95.5% and 20% of patients with definitive and atypical cataplexy, respectively...
September 9, 2016: Sleep
https://www.readbyqxmd.com/read/27634789/cerebrospinal-fluid-biomarkers-of-neurodegeneration-are-decreased-or-normal-in-narcolepsy
#19
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 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)...
September 9, 2016: Sleep
https://www.readbyqxmd.com/read/27634355/glyx-13-produces-rapid-antidepressant-responses-with-key-synaptic-and-behavioral-effects-distinct-from-ketamine
#20
Rong-Jian Liu, Catharine Duman, Taro Kato, Brendan Hare, Dora Lopresto, Eunyoung Bang, Jeffery Burgdorf, Joseph Moskal, Jane Taylor, George Aghajanian, Ronald S Duman
GLYX-13 is a putative NMDA receptor modulator with glycine-site partial agonist properties that produces rapid antidepressant effects, but without the psychotomimetic side effects of ketamine. Studies were conducted to examine the molecular, cellular, and behavioral actions of GLYX-13 to further characterize the mechanisms underlying the antidepressant actions of this agent. The results demonstrate that a single dose of GLYX-13 rapidly activates the mTORC1 pathway in the prefrontal cortex (PFC), and that infusion of the selective mTORC1 inhibitor rapamycin into the medial PFC (mPFC) blocks the antidepressant behavioral actions of GLYX-13, indicating a requirement for mTORC1 similar to ketamine...
October 19, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
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