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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/27909989/orexin-and-central-modulation-of-cardiovascular-and-respiratory-function
#4
Pascal Carrive, Tomoyuki Kuwaki
Orexin makes an important contribution to the regulation of cardiorespiratory function. When injected centrally under anesthesia, orexin increases blood pressure, heart rate, sympathetic nerve activity, and the amplitude and frequency of respiration. This is consistent with the location of orexin neurons in the hypothalamus and the distribution of orexin terminals at all levels of the central autonomic and respiratory network. These cardiorespiratory responses are components of arousal and are necessary to allow the expression of motivated behaviors...
December 2, 2016: Current Topics in Behavioral Neurosciences
https://www.readbyqxmd.com/read/27909987/orexin-ox2-receptor-antagonists-as-sleep-aids
#5
Laura H Jacobson, Sui Chen, Sanjida Mir, Daniel Hoyer
The discovery of the orexin system represents the single major progress in the sleep field of the last three to four decades. The two orexin peptides and their two receptors play a major role in arousal and sleep/wake cycles. Defects in the orexin system lead to narcolepsy with cataplexy in humans and dogs and can be experimentally reproduced in rodents. At least six orexin receptor antagonists have reached Phase II or Phase III clinical trials in insomnia, five of which are dual orexin receptor antagonists (DORAs) that target both OX1 and OX2 receptors (OX2Rs)...
December 2, 2016: Current Topics in Behavioral Neurosciences
https://www.readbyqxmd.com/read/27906750/role-of-orexin-2-and-cb1-receptors-within-the-periaqueductal-gray-matter-in-lateral-hypothalamic-induced-antinociception-in-rats
#6
Mohammad-Hossein Esmaeili, Zahra Reisi, Somayeh Ezzatpanah, Abbas Haghparast
Orexin plays an important role in pain modulation. Orexin-1 and orexin-2 receptors (Ox1r and Ox2r) are found at high density in the ventrolateral periaqueductal gray matter (vlPAG). Our previous study showed that chemical stimulation of the lateral hypothalamus with carbachol induces antinociception in the tail-flick test, a model of acute pain, and Ox1r-mediated antinociception in the vlPAG is modulated by the activity of vlPAG CB1 receptors. In the current study, TCS OX2 29, an Ox2r antagonist (5, 15, 50, 150, and 500 nmol/l), was microinjected into the vlPAG 5 min before the administration of carbachol (125 nmol/l)...
November 30, 2016: Behavioural Pharmacology
https://www.readbyqxmd.com/read/27898425/modulation-of-microbiota-gut-brain-axis-by-berberine-resulting-in-improved-metabolic-status-in-high-fat-diet-fed-rats
#7
Honglin Sun, Ningjian Wang, Zhen Cang, Chaoxia Zhu, Li Zhao, Xiaomin Nie, Jing Cheng, Fangzhen Xia, Hualing Zhai, Yingli Lu
OBJECTIVE: To investigate whether or not berberine could improve metabolic status of high-fat-fed rats through modulation of microbiota-gut-brain axis. METHODS: Berberine was administered on high-fat-fed Sprague-Dawley rats. Brain-gut hormones were detected, and changes of gut microbiota were analyzed by 16S rRNA gene sequencing. RESULTS: Berberine could reduce weight gain and lipolysis in the high-fat diet-fed group. Moreover, trends of ameliorated insulin resistance and decreased endogenous glucose production were observed...
November 30, 2016: Obesity Facts
https://www.readbyqxmd.com/read/27876121/possible-neuronal-mechanisms-of-sleep-disturbances-in-patients-with-autism-spectrum-disorders-and-attention-deficit-hyperactivity-disorder
#8
Jun Kohyama
The most common form of sleep disturbance among both patients with autism spectrum disorders and patients with attention-deficit/hyperactivity disorder is sleep-onset insomnia, but the neuronal mechanisms underlying it have yet to be elucidated and no specific treatment strategy has been proposed. This means that many caregivers struggle to manage this problem on a daily basis. This paper presents a hypothesis about the neuronal mechanisms underlying insomnia in patients with autism spectrum disorders and attention-deficit/hyperactivity disorder based on recent clinical and basic research...
December 2016: Medical Hypotheses
https://www.readbyqxmd.com/read/27860547/the-discovery-of-suvorexant-the-first-orexin-receptor-drug-for-insomnia
#9
Paul J Coleman, Anthony L Gotter, W Joseph Herring, Christopher J Winrow, John J Renger
Historically, pharmacological therapies have used mechanisms such as γ- aminobutyric acid A (GABAA) receptor potentiation to drive sleep through broad suppression of central nervous system activity. With the discovery of orexin signaling loss as the etiology underlying narcolepsy, a disorder associated with hypersomnolence, orexin antagonism emerged as an alternative approach to attenuate orexin-induced wakefulness more selectively. Dual orexin receptor antagonists (DORAs) block the activity of orexin 1 and 2 receptors to both reduce the threshold to transition into sleep and attenuate orexin-mediated arousal...
November 17, 2016: Annual Review of Pharmacology and Toxicology
https://www.readbyqxmd.com/read/27853416/neuropeptide-control-of-feeding-behavior-in-birds-and-its-difference-with-mammals
#10
REVIEW
Tetsuya Tachibana, Kazuyoshi Tsutsui
Feeding is an essential behavior for animals to sustain their lives. Over the past several decades, many neuropeptides that regulate feeding behavior have been identified in vertebrates. These neuropeptides are called "feeding regulatory neuropeptides." There have been numerous studies on the role of feeding regulatory neuropeptides in vertebrates including birds. Some feeding regulatory neuropeptides show different effects on feeding behavior between birds and other vertebrates, particularly mammals. The difference is marked with orexigenic neuropeptides...
2016: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/27845440/odour-induced-analgesia-mediated-by-hypothalamic-orexin-neurons-in-mice
#11
Shogo Tashiro, Ran Yamaguchi, Sodemi Ishikawa, Takeshi Sakurai, Katsuko Kajiya, Yuichi Kanmura, Tomoyuki Kuwaki, Hideki Kashiwadani
Various folk remedies employ certain odorous compounds with analgesic effects. In fact, linalool, a monoterpene alcohol found in lavender extracts, has been found to attenuate pain responses via subcutaneous, intraperitoneal, intrathecal, and oral administration. However, the analgesic effects of odorous compounds mediated by olfaction have not been thoroughly examined. We performed behavioural pain tests under odourant vapour exposure in mice. Among six odourant molecules examined, linalool significantly increased the pain threshold and attenuated pain behaviours...
November 15, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27837432/orexin-a-promotes-glu-uptake-by-ox1r-pkc%C3%AE-erk1-2-glt-1-pathway-in-astrocytes-and-protects-co-cultured-astrocytes-and-neurons-against-apoptosis-in-anoxia-hypoglycemic-injury-in-vitro
#12
Qing Shu, Jianhuai Zhang, Wei Ma, Youying Lei, Dan Zhou
Orexin-A, which is an endogenous neuropeptide, is reported to have a protective role in ischemic stroke. High-concentration glutamic acid (Glu) induced by hypoxia injury in ischemic stroke can be inhibited by glial glutamate transporter GLT-1 which is only expressed in astroglia cells. A previous study reported that Orexin-A may regulate GLT-1 expression. However, the role of orexin-A in the regulation of GLT-1 in ischemic stroke still remains unclear. In this study, we aimed to investigate the effect and the underlying mechanism of orexin-A on Glu uptake in astrocytes in vitro and this effect on protecting the neurons from anoxia/hypoglycemic injury...
November 12, 2016: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/27830577/orexin-hypocretin-and-organizing-principles-for-a-diversity-of-wake-promoting-neurons-in-the-brain
#13
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/27825624/quantification-of-suvorexant-in-urine-using-gas-chromatography-mass-spectrometry
#14
Mariah Carson, Sarah Kerrigan
Suvorexant (Belsomra(®)) is a novel sedative hypnotic drug that is prescribed to promote sleep in patients with insomnia. It is the first of a new class of drugs classified as dual orexin receptor antagonists (DORAs). Sedative hypnotics with central nervous system depressant effects feature prominently in forensic toxicology investigations. For this reason, a new analytical method was developed to identify suvorexant in urine using liquid-liquid extraction (LLE) and gas chromatography/mass spectrometry (GC/MS)...
November 2, 2016: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/27824065/optogenetic-activation-of-serotonergic-terminals-facilitates-gabaergic-inhibitory-input-to-orexin-hypocretin-neurons
#15
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/27821550/high-dimensional-single-cell-analysis-reveals-the-immune-signature-of-narcolepsy
#16
Felix J Hartmann, Raphaël Bernard-Valnet, Clémence Quériault, Dunja Mrdjen, Lukas M Weber, Edoardo Galli, Carsten Krieg, Mark D Robinson, Xuan-Hung Nguyen, Yves Dauvilliers, Roland S Liblau, Burkhard Becher
Narcolepsy type 1 is a devastating neurological sleep disorder resulting from the destruction of orexin-producing neurons in the central nervous system (CNS). Despite its striking association with the HLA-DQB1*06:02 allele, the autoimmune etiology of narcolepsy has remained largely hypothetical. Here, we compared peripheral mononucleated cells from narcolepsy patients with HLA-DQB1*06:02-matched healthy controls using high-dimensional mass cytometry in combination with algorithm-guided data analysis. Narcolepsy patients displayed multifaceted immune activation in CD4(+) and CD8(+) T cells dominated by elevated levels of B cell-supporting cytokines...
November 14, 2016: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27818110/discovery-of-highly-potent-and-selective-orexin-1-receptor-antagonists-1-soras-suitable-for-in-vivo-interrogation-of-orexin-1-receptor-pharmacology
#17
Craig A Stump, Andrew J Cooke, Joseph Bruno, Tamara D Cabalu, Anthony L Gotter, C Meacham Harell, Scott D Kuduk, Terrence P McDonald, Julie O'Brien, John J Renger, Peter D Williams, Christopher J Winrow, Paul J Coleman
While a correlation between blockade of the orexin 2 receptor (OX2R) with either a dual orexin receptor antagonist (DORA) or a selective orexin 2 receptor antagonist (2-SORA) and a decrease of wakefulness is well established, less is known about selective blockade of the orexin 1 receptor (OX1R). Therefore, a highly selective orexin 1 antagonist (1-SORA) with suitable properties to allow in vivo interrogation of OX1R specific pharmacology in preclinical species remains an attractive target. Herein, we describe the discovery of an optimized 1-SORA series in the piperidine ether class...
October 14, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27816550/intra-lc-microinjection-of-orexin-type-1-receptor-antagonist-sb-334867-attenuates-the-expression-of-glutamate-induced-opiate-withdrawal-like-signs-during-the-active-phase-in-rats
#18
Bita Hooshmand, Hossein Azizi, Mohammad Javan, Saeed Semnanian
Opiate withdrawal syndrome is temporally associated with the hyperactivity of locus coeruleus neurons. Previous studies have shown that this hyperactivity, at least in part, results from the activity of excitatory afferents which mainly include the orexinergic neurons of hypothalamus and glutamatergic neurons of paragigantocellularis (PGi) nucleus. The effect of intra LC orexin type 1 receptor antagonism were investigated on expression of glutamate-induced morphine withdrawal-like signs in rats. Regarding the involvement of both orexin and LC in modulation of circadian rhythm, experimental procedures were performed during the rest (day) and the active (night) phases...
November 2, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/27815840/application-of-the-co-culture-membrane-system-pointed-to-a-protective-role-of-catestatin-on-hippocampal-plus-hypothalamic-neurons-exposed-to-oxygen-and-glucose-deprivation
#19
Maria Mele, Sabrina Morelli, Gilda Fazzari, Ennio Avolio, Raffaella Alò, Antonella Piscioneri, Loredana De Bartolo, Rosa Maria Facciolo, Marcello Canonaco
Depletion of oxygen and glucose even for brief periods is sufficient to cause cerebral ischemia, which is a predominant worldwide cause of motor deficits with the reduction of life quality and subsequently death. Hence, more insights regarding protective measures against ischemic events are becoming a major research goal. Among the many neuronal factors, N-methyl-D-aspartate receptors (NMDAR), orexinergic neuroreceptors (ORXR), and sympatho-inhibitory neuropeptide catestatin (CST) are widely involved with ischemic episodes...
November 5, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27814668/orexin-a-protects-human-neuroblastoma-sh-sy5y-cells-against-6-ohda-induced-neurotoxicity-involvement-of-pkc-and-pi3k-signaling-pathways
#20
Hamzeh Pasban-Aliabadi, Saeed Esmaeili-Mahani, Mehdi Abbasnejad
Parkinson's disease (PD) is a common neurodegenerative disorder characterized by progressive and selective death of dopaminergic neurons. Multifunctional neuropeptide orexin-A is involved in many biological events of the body. It has been shown that orexin-A has protective effects in neurodegenerative disease such as PD. However, its cellular mechanisms have not yet been fully clarified. Here, we investigated the intracellular signaling pathway of orexin-A neuroprotection in 6-OHDA-induced SH-SY5H cells damage as an in vitro model of PD...
November 4, 2016: Rejuvenation Research
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