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Hypocretin

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https://www.readbyqxmd.com/read/29038792/neuroanatomical-relationships-between-orexin-hypocretin-containing-neurons-nerve-fibers-and-nicotine-induced-c-fos-activated-cells-of-the-reward-addiction-neurocircuitry
#1
Ozra Dehkordi, Jed E Rose, Martha I Dávila-García, Richard M Millis, Samar Ali Mirzaei, Kebreten F Manaye, Annapurni Jayam-Trouth
Orexin/hypocretin-containing neurons in lateral hypothalamus (LH) are implicated in the neurobiology of nicotine addiction. However, the neuroanatomical relationships between orexin-neurons/nerve fibers and nicotine-activated cells within the reward-addiction neurocircuitry is not known. In the present study in mice, we first used c-Fos immunohistochemistry to identify CNS cells stimulated by an acute single injection of nicotine (NIC, 2 mg/kg, IP). Sequential double-labelling was then performed to identify the location of orexin-containing neurons and nerve fibers with respect to NIC-induced c-Fos activated cells and/or tyrosine hydroxylase (TH) immunoreactive (IR) cells of the mesocorticolimbic reward-addiction pathways...
August 2017: Journal of Alcoholism and Drug Dependence
https://www.readbyqxmd.com/read/29029348/dysregulation-of-sleep-behavioral-states-in-narcolepsy
#2
Sarah F Schoch, Esther Werth, Rositsa Poryazova, Thomas E Scammell, Christian R Baumann, Lukas L Imbach
Study Objectives: Patients with narcolepsy suffer from poor maintenance of wakefulness and fragmented night sleep, but the underlying mechanism of sleep boundary dysregulation remains little understood. The goal of this study was to quantify abnormal sleep-wake regulation in narcolepsy patients. Methods: Using a model-based approach (state space analysis), we analyzed overnight EEG recordings in ten patients with narcolepsy type 1 and age- and gender-matched healthy control subjects...
October 5, 2017: Sleep
https://www.readbyqxmd.com/read/28991183/orexin-receptor-multimerization-versus-functional-interactions-neuropharmacological-implications-for-opioid-and-cannabinoid-signalling-and-pharmacogenetics
#3
Miles D Thompson, Takeshi Sakurai, Innocenzo Rainero, Mary C Maj, Jyrki P Kukkonen
Orexins/hypocretins are neuropeptides formed by proteolytic cleavage of a precursor peptide, which are produced by neurons found in the lateral hypothalamus. The G protein-coupled receptors (GPCRs) for these ligands, the OX₁ and OX₂ orexin receptors, are more widely expressed throughout the central nervous system. The orexin/hypocretin system has been implicated in many pathways, and its dysregulation is under investigation in a number of diseases. Disorders in which orexinergic mechanisms are being investigated include narcolepsy, idiopathic sleep disorders, cluster headache and migraine...
October 8, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28991006/autoimmunity-in-narcolepsy
#4
Melodie Bonvalet, Hanna M Ollila, Aditya Ambati, Emmanuel Mignot
PURPOSE OF REVIEW: Summarize the recent findings in narcolepsy focusing on the environmental and genetic risk factors in disease development. RECENT FINDINGS: Both genetic and epidemiological evidence point towards an autoimmune mechanism in the destruction of orexin/hypocretin neurons. Recent studies suggest both humoral and cellular immune responses in the disease development. SUMMARY: Narcolepsy is a severe sleep disorder, in which neurons producing orexin/hypocretin in the hypothalamus are destroyed...
November 2017: Current Opinion in Pulmonary Medicine
https://www.readbyqxmd.com/read/28975007/the-medical-and-economic-burden-of-narcolepsy-implications-for-managed-care
#5
REVIEW
Michael J Thorpy, George Hiller
BACKGROUND: The neurologic disorder narcolepsy results from dysregulation of the sleep-wake cycle and is primarily characterized by chronic, severely excessive daytime sleepiness and cataplexy, an emotionally induced muscle weakness. The prevalence of narcolepsy is approximately 0.05%, and onset generally occurs during the first 2 decades of life. Narcolepsy is believed to be an autoimmune disorder with destruction of hypocretin-producing neurons in the lateral hypothalamus. OBJECTIVES: To provide an enhanced understanding of narcolepsy and establish the need for early diagnosis and rapid initiation of effective treatment for patients with narcolepsy...
July 2017: American Health & Drug Benefits
https://www.readbyqxmd.com/read/28971565/hypocretin-receptor-1-knockdown-in-the-ventral-tegmental-area-attenuates-mesolimbic-dopamine-signaling-and-reduces-motivation-for-cocaine
#6
David L Bernstein, Preeti S Badve, Jessica R Barson, Caroline E Bass, Rodrigo A España
The hypocretin receptor 1 (HCRTr1) is a critical participant in the regulation of motivated behavior. Previous observations demonstrate that acute pharmacological blockade of HCRTr1 disrupts dopamine (DA) signaling and the motivation for cocaine when delivered systemically or directly into the ventral tegmental area (VTA). To further examine the involvement of HCRTr1 in regulating reward and reinforcement processing, we employed an adeno-associated virus to express a short hairpin RNA designed to knock down HCRTr1...
October 2, 2017: Addiction Biology
https://www.readbyqxmd.com/read/28966976/neurochemical-heterogeneity-among-lateral-hypothalamic-hypocretin-orexin-and-melanin-concentrating-hormone-neurons-identified-through-single-cell-gene-expression-analysis
#7
Laura E Mickelsen, Fredrick W Kolling, Brock R Chimileski, Akie Fujita, Carol Norris, Kun Chen, Craig E Nelson, Alexander C Jackson
The lateral hypothalamic area (LHA) lies at the intersection of multiple neural and humoral systems and orchestrates fundamental aspects of behavior. Two neuronal cell types found in the LHA are defined by their expression of hypocretin/orexin (Hcrt/Ox) and melanin-concentrating hormone (MCH) and are both important regulators of arousal, feeding, and metabolism. Conflicting evidence suggests that these cell populations have a more complex signaling repertoire than previously appreciated, particularly in regard to their coexpression of other neuropeptides and the machinery for the synthesis and release of GABA and glutamate...
September 2017: ENeuro
https://www.readbyqxmd.com/read/28966744/human-hypocretin-deficient-narcolepsy-aberrant-food-choice-due-to-impaired-taste
#8
Giselle de Martin Truzzi, Renata Carvalho Cremaschi, Fernando Morgadinho Coelho
Authors demonstrate that patients with narcolepsy type 1 (N1) have more tendency of eat salty snacks after satiety than health volunteers. A few mechanisms to explain the weight gain have been discussed in narcolepsy. The hypocretin-1 deficiency can influence the olfactory system. The olfactory system should be modulated through hypocretin-1 via connections from the hypothalamic to other brain regions. Likewise, hypocretin-1 can be synthesized locally in our olfactory mucosa with possible private role modulating the olfactory...
April 2017: Sleep Science
https://www.readbyqxmd.com/read/28956242/polysomnographic-findings-in-craniopharyngioma-patients
#9
Line Pickering, Marianne Klose, Ulla Feldt-Rasmussen, Poul Jennum
PURPOSE: The purpose of this study is to evaluate whether damage to the hypothalamus due to craniopharyngioma or consequent surgery may involve the sleep-wake regulatory system, resulting in sleep disturbances and sleepiness. METHODS: Seven craniopharyngioma patients and 10 healthy controls were evaluated with sleep questionnaires including the Epworth Sleepiness Scale, polysomnography, and a multiple sleep latency test (MSLT). Five patients and eight controls had lumbar puncture performed to determine hypocretin-1 levels...
September 27, 2017: Sleep & Breathing, Schlaf & Atmung
https://www.readbyqxmd.com/read/28940143/narcolepsy-type-1-as-an-autoimmune-disorder-evidence-and-implications-for-pharmacological-treatment
#10
Lucie Barateau, Roland Liblau, Christelle Peyron, Yves Dauvilliers
Narcolepsy type 1 (NT1) is a rare sleep disorder caused by the very specific loss of hypothalamic hypocretin (Hcrt)/orexin neurons. The exact underlying process leading to this destruction is yet unknown, but indirect evidence strongly supports an autoimmune origin. The association with immune-related genetic factors, in particular the strongest association ever reported in a disease with an allele of a human leukocyte antigen (HLA) gene, and with environmental factors (i.e., the H1N1 influenza infection and vaccination during the pandemic in 2009) are in favor of such a hypothesis...
September 22, 2017: CNS Drugs
https://www.readbyqxmd.com/read/28899014/slow-wave-sleep-disruption-increases-cerebrospinal-fluid-amyloid-%C3%AE-levels
#11
Yo-El S Ju, Sharon J Ooms, Courtney Sutphen, Shannon L Macauley, Margaret A Zangrilli, Gina Jerome, Anne M Fagan, Emmanuel Mignot, John M Zempel, Jurgen A H R Claassen, David M Holtzman
See Mander et al. (doi:10.1093/awx174) for a scientific commentary on this article.Sleep deprivation increases amyloid-β, suggesting that chronically disrupted sleep may promote amyloid plaques and other downstream Alzheimer's disease pathologies including tauopathy or inflammation. To date, studies have not examined which aspect of sleep modulates amyloid-β or other Alzheimer's disease biomarkers. Seventeen healthy adults (age 35-65 years) without sleep disorders underwent 5-14 days of actigraphy, followed by slow wave activity disruption during polysomnogram, and cerebrospinal fluid collection the following morning for measurement of amyloid-β, tau, total protein, YKL-40, and hypocretin...
August 1, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28847002/lhx6-positive-gaba-releasing-neurons-of-the-zona-incerta-promote-sleep
#12
Kai Liu, Juhyun Kim, Dong Won Kim, Yi Stephanie Zhang, Hechen Bao, Myrto Denaxa, Szu-Aun Lim, Eileen Kim, Chang Liu, Ian R Wickersham, Vassilis Pachinis, Samer Hattar, Juan Song, Solange P Brown, Seth Blackshaw
Multiple populations of wake-promoting neurons have been characterized in mammals, but few sleep-promoting neurons have been identified. Wake-promoting cell types include hypocretin and GABA (γ-aminobutyric-acid)-releasing neurons of the lateral hypothalamus, which promote the transition to wakefulness from non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. Here we show that a subset of GABAergic neurons in the mouse ventral zona incerta, which express the LIM homeodomain factor Lhx6 and are activated by sleep pressure, both directly inhibit wake-active hypocretin and GABAergic cells in the lateral hypothalamus and receive inputs from multiple sleep-wake-regulating neurons...
August 31, 2017: Nature
https://www.readbyqxmd.com/read/28809797/optogenetic-investigation-of-arousal-circuits
#13
REVIEW
Susan M Tyree, Luis de Lecea
Modulation between sleep and wake states is controlled by a number of heterogeneous neuron populations. Due to the topological proximity and genetic co-localization of the neurons underlying sleep-wake state modulation optogenetic methods offer a significant improvement in the ability to benefit from both the precision of genetic targeting and millisecond temporal control. Beginning with an overview of the neuron populations mediating arousal, this review outlines the progress that has been made in the investigation of arousal circuits since the incorporation of optogenetic techniques and the first in vivo application of optogenetic stimulation in hypocretin neurons in the lateral hypothalamus...
August 15, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28777177/chronic-insomnia-disorder
#14
Alon Y Avidan, David N Neubauer
PURPOSE OF REVIEW: Neurologists, along with all health care providers, commonly encounter patients with insomnia, which is a condition that impacts patients' underlying neurologic conditions in a bidirectional manner. While chronic insomnia is one of the most common sleep disturbances, only a small proportion of individuals with this condition discuss their sleep problems with their providers. When insomnia is described, it is more often in relationship to another medical problem, as opposed to an independent condition...
August 2017: Continuum: Lifelong Learning in Neurology
https://www.readbyqxmd.com/read/28777172/narcolepsy-and-other-central-hypersomnias
#15
Yves Dauvilliers, Lucie Barateau
PURPOSE OF REVIEW: This article focuses on the clinical presentation, pathophysiology, diagnosis, differential diagnosis, and management of narcolepsy type 1 and narcolepsy type 2, idiopathic hypersomnia, Kleine-Levin syndrome, and other central disorders of hypersomnolence, as defined in the International Classification of Sleep Disorders, Third Edition (ICSD-3). RECENT FINDINGS: In ICSD-3, the names of some central disorders of hypersomnolence have been changed: narcolepsy with cataplexy and narcolepsy without cataplexy have been renamed narcolepsy type 1 and narcolepsy type 2, respectively...
August 2017: Continuum: Lifelong Learning in Neurology
https://www.readbyqxmd.com/read/28763482/attention-impairments-and-adhd-symptoms-in-adult-narcoleptic-patients-with-and-without-hypocretin-deficiency
#16
Marco Filardi, Fabio Pizza, Lorenzo Tonetti, Elena Antelmi, Vincenzo Natale, Giuseppe Plazzi
BACKGROUND: Attentional complaints are common in narcolepsy patients and can overlap with daytime sleepiness features. Few studies attempted to characterize attentional domains in narcolepsy leading to controversial results. We aimed to assess the impact of hypocretin deficiency on attentional functioning by comparing performances on the attention network test (ANT) of narcoleptic patients with hypocretin deficiency (narcolepsy type 1-NT1) versus patients without hypocretin deficiency (narcolepsy type 2-NT2) and healthy controls...
2017: PloS One
https://www.readbyqxmd.com/read/28762874/reactivation-of-hyperglycemia-induced-hypocretin-hcrt-gene-silencing-by-n-acetyl-d-mannosamine-in-the-orexin-neurons-derived-from-human-ips-cells
#17
Koji Hayakawa, Yasuharu Sakamoto, Osamu Kanie, Atsuko Ohtake, Shusaku Daikoku, Yukishige Ito, Kunio Shiota
Orexin neurons regulate critical brain activities for controlling sleep, eating, emotions, and metabolism, and impaired orexin neuron function results in several neurological disorders. Therefore, restoring normal orexin function and understanding the mechanisms of loss or impairment of orexin neurons represent important goals. As a step toward that end, we generated human orexin neurons from induced pluripotent stem cells (hiPSCs) by treatment with N-acetyl-d-mannosamine (ManNAc) and its derivatives. The generation of orexin neurons was associated with DNA hypomethylation, histone H3/H4 hyperacetylation, and hypo-O-GlcNAcylation on the HCRT gene locus, and, thereby, the treatment of inhibitors of SIRT1 and OGT were effective at inducing orexin neurons from hiPSCs...
August 1, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28741623/effects-of-suvorexant-a-dual-orexin-hypocretin-receptor-antagonist-on-impulsive-behavior-associated-with-cocaine
#18
Taylor A Gentile, Steven J Simmons, Mia N Watson, Krista L Connelly, Eugen Brailoiu, Yanan Zhang, John W Muschamp
Hypothalamic hypocretin (orexin) peptides mediate arousal, attention, and reward processing. Fibers containing orexins project to brain structures that govern motivated behavior, including the ventral tegmental area (VTA). A number of psychiatric conditions, including attention deficit hyperactivity disorder (ADHD) and substance use disorders, are characterized by deficits in impulse control, however the relationship between orexin and impulsive behavior is incompletely characterized. The effects of systemic or centrally administered orexin receptor (OXR) antagonists on measures of impulsive-like behavior in rats were evaluated using the five-choice serial reaction time task (5-CSRTT) and delay discounting procedures...
July 25, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28738331/future-perspectives-in-sleep-medicine
#19
Leh-Kiong Anne Huon, Christian Guilleminault
"Sleep Medicine" is now a specialty in its own right. Currently, there is increasing recognition of the very negative impact sleep disorders have on learning, education, safety, and quality of life. Technological advances will help us to break down diagnoses (e.g., narcolepsy has now been subdivided into types 1 and 2, depending upon the hypocretin levels in the spinal fluid) and to discover relationships to other bodily systems (e.g., type 1 narcolepsy potentially being an autoimmune disorder). The modern lifestyle of many, as characterized by a shortening of sleep periods, shift work, jet lag, and the need to be constantly available, means that advances in sleep medicine may result in a major understanding of more balanced "work-rest lifestyle" modifications...
2017: Advances in Oto-rhino-laryngology
https://www.readbyqxmd.com/read/28729827/lateral-hypothalamic-control-of-the-ventral-tegmental-area-reward-evaluation-and-the-driving-of-motivated-behavior
#20
REVIEW
Susan M Tyree, Luis de Lecea
The lateral hypothalamus (LH) plays an important role in many motivated behaviors, sleep-wake states, food intake, drug-seeking, energy balance, etc. It is also home to a heterogeneous population of neurons that express and co-express multiple neuropeptides including hypocretin (Hcrt), melanin-concentrating hormone (MCH), cocaine- and amphetamine-regulated transcript (CART) and neurotensin (NT). These neurons project widely throughout the brain to areas such as the locus coeruleus, the bed nucleus of the stria terminalis, the amygdala and the ventral tegmental area (VTA)...
2017: Frontiers in Systems Neuroscience
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