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https://www.readbyqxmd.com/read/28108192/epidemiology-and-pathophysiology-of-childhood-narcolepsy
#1
REVIEW
Thomas J Dye, Neepa Gurbani, Narong Simakajornboon
It is now recognized that there are two types of narcolepsy. Narcolepsy type I or Narcolepsy with cataplexy is caused by the loss of hypocretin or orexin neurons. Narcolepsy type II or narcolepsy without cataplexy has normal hypocretin and the etiology is unknown. Hypocretin is a neuropeptide produced by neurons in the lateral hypothalamus. Both genetic and environmental factors play a crucial role in the pathogenesis of narcolepsy. Most patients with narcolepsy type I and half of patients with narcolepsy type II carry HLA-DQB1*0602...
December 21, 2016: Paediatric Respiratory Reviews
https://www.readbyqxmd.com/read/28105535/the-neuropeptide-orexin-a-inhibits-the-gabaa-receptor-by-pkc-and-ca-2-camkii-dependent-phosphorylation-of-its-%C3%AE-1-subunit
#2
Divya Sachidanandan, Haritha P Reddy, Anitha Mani, Geoffrey J Hyde, Amal Kanti Bera
Orexin-A and orexin-B (Ox-A, Ox-B) are neuropeptides produced by a small number of neurons that originate in the hypothalamus and project widely in the brain. Only discovered in 1998, the orexins are already known to regulate several behaviours. Most prominently, they help to stabilise the waking state, a role with demonstrated significance in the clinical management of narcolepsy and insomnia. Orexins bind to G-protein-coupled receptors (predominantly postsynaptic) of two subtypes, OX1R and OX2R. The primary effect of Ox-OXR binding is a direct depolarising influence mediated by cell membrane cation channels, but a wide variety of secondary effects, both pre- and postsynaptic, are also emerging...
January 19, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28100828/an-integrated-modelling-framework-for-neural-circuits-with-multiple-neuromodulators
#3
Alok Joshi, Vahab Youssofzadeh, Vinith Vemana, T M McGinnity, Girijesh Prasad, KongFatt Wong-Lin
Neuromodulators are endogenous neurochemicals that regulate biophysical and biochemical processes, which control brain function and behaviour, and are often the targets of neuropharmacological drugs. Neuromodulator effects are generally complex partly owing to the involvement of broad innervation, co-release of neuromodulators, complex intra- and extrasynaptic mechanism, existence of multiple receptor subtypes and high interconnectivity within the brain. In this work, we propose an efficient yet sufficiently realistic computational neural modelling framework to study some of these complex behaviours...
January 2017: Journal of the Royal Society, Interface
https://www.readbyqxmd.com/read/28097729/the-role-of-orexin-signaling-in-the-ventral-tegmental-area-and-central-amygdala-in-modulating-binge-like-ethanol-drinking-behavior
#4
Jeffrey J Olney, Montserrat Navarro, Todd E Thiele
BACKGROUND: Recent reports have demonstrated that binge-like ethanol drinking leads to an increase in hypothalamic orexin (OX) signaling and that suppressing this signaling via systemic administration of an orexin receptor (OXR) antagonist blocks this behavior; however, the specific OX pathways that modulate this behavior remain unknown. The goal of the present study was to further elucidate the role of the OX system in binge-like ethanol drinking using behavioral, molecular, and pharmacological techniques...
January 17, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28093335/intracoerulear-microinjection-of-orexin-a-induces-morphine-withdrawal-like-signs-in-rats
#5
Masoumeh Ghaemi-Jandabi, Hossein Azizi, S Mohammad Ahmadi-Soleimani, Saeed Semnanian
Orexin (hypocretin) neuropeptides play a pivotal role in expression of opioid withdrawal signs. Hypothalamic orexinergic neurons provide dense afferents for the nucleus locus coeruleus (LC). Somatic signs of opioid withdrawal are associated with the enhanced activity of LC neurons. In addition, intra-LC administration of orexin-A leads to the hyperactivity of LC neurons. The present study was an attempt to investigate whether intra-LC microinjection of orexin-A induces morphine withdrawal-like signs in both morphine dependent and control rats...
January 13, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28089263/adiponectin-orexin-a-and-orexin-b-concentrations-in-the-serum-and-uterine-luminal-fluid-during-early-pregnancy-of-pigs
#6
Nina Smolinska, Marta Kiezun, Kamil Dobrzyn, Karol Szeszko, Anna Maleszka, Tadeusz Kaminski
Adiponectin is the most abundant adipose-released protein that circulates in human plasma at high concentrations. The neuropeptides orexin A (OXA, hypocretin-1) and orexin B (OXB, hypocretin-2) are derived from a common precursor peptide, prepro-orexin and are produced mainly by neurons located in the lateral hypothalamus. It has been demonstrated that the peptides such as adiponectin and orexins have an important role in the regulation of energy metabolism and neuroendocrine functions. These hormones appear to be implicated in both normal and disturbed pregnancy...
January 9, 2017: Animal Reproduction Science
https://www.readbyqxmd.com/read/28080173/evaluation-of-long-term-cryostorage-of-brain-tissue-sections-for-quantitative-histochemistry
#7
Larissa I Estrada, Amy A Robinson, Ana C Amaral, Eustathia L Giannaris, Nadine C Heyworth, Farzad Mortazavi, Laura B Ngwenya, Debra E Roberts, Howard J Cabral, Ronald J Killiany, Douglas L Rosene
Storage of tissue sections for long periods allows multiple samples, acquired over months or years, to be processed together, in the same reagents, for quantitative histochemical studies. Protocols for freezer storage of free-floating frozen sections using sucrose with different additives have been reported and assert that storage has no effect on histochemistry, but no quantitative support has been provided. The present study analyzed the efficacy of long-term storage of brain tissue sections at -80C in buffered 15% glycerol...
January 1, 2017: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
https://www.readbyqxmd.com/read/28075519/an-update-of-management-of-insomnia-in-patients-with-chronic-orofacial-pain
#8
REVIEW
Galit Almoznino, Yaron Haviv, Yair Sharav, Rafael Benoliel
In this review we discuss the management of chronic orofacial pain (COFP) patients with insomnia. Diagnostic work-up and follow-up routines of COFP patients should include assessment of sleep problems. Management is based on a multidisciplinary approach, addressing the factors that modulate the pain experience as well as insomnia and including both non-pharmacological and pharmacological modalities. Parallel to treatment, patients should receive therapy for co-morbid medical and psychiatric disorders, and possible substance abuse that may be that may trigger or worsen the COFP and/or their insomnia...
January 11, 2017: Oral Diseases
https://www.readbyqxmd.com/read/28072416/preclinical-amyloid-pathology-biomarker-positivity-effects-on-tau-pathology-and-neurodegeneration
#9
K Höglund, S Kern, A Zettergren, A Börjesson-Hansson, H Zetterberg, I Skoog, K Blennow
Brain autopsy and biomarker studies indicate that the pathology of Alzheimer's disease (AD) is initiated at least 10-20 years before clinical symptoms. This provides a window of opportunity to initiate preventive treatment. However, this emphasizes the necessity for biomarkers that identify individuals at risk for developing AD later in life. In this cross-sectional study, originating from three epidemiologic studies in Sweden (n=1428), the objective was to examine whether amyloid pathology, as determined by low cerebrospinal fluid (CSF) concentration of the 42 amino acid form of β-amyloid (Aβ42), is associated with biomarker evidence of other pathological changes in cognitively healthy elderly...
January 10, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28061506/role-of-rem-sleep-melanin-concentrating-hormone-and-orexin-hypocretin-systems-in-the-sleep-deprivation-pre-ischemia
#10
Marta Pace, Antoine Adamantidis, Laura Facchin, Claudio Bassetti
STUDY OBJECTIVES: Sleep reduction after stroke is linked to poor recovery in patients. Conversely, a neuroprotective effect is observed in animals subjected to acute sleep deprivation (SD) before ischemia. This neuroprotection is associated with an increase of the sleep, melanin concentrating hormone (MCH) and orexin/hypocretin (OX) systems. This study aims to 1) assess the relationship between sleep and recovery; 2) test the association between MCH and OX systems with the pathological mechanisms of stroke...
2017: PloS One
https://www.readbyqxmd.com/read/28054308/inhibition-of-ghrelin-induced-feeding-in-rats-by-pretreatment-with-a-novel-dual-orexin-receptor-antagonist
#11
Mariko So, Hirofumi Hashimoto, Reiko Saito, Yukiyo Yamamoto, Yasuhito Motojima, Hiromichi Ueno, Satomi Sonoda, Mitsuhiro Yoshimura, Takashi Maruyama, Koichi Kusuhara, Yoichi Ueta
Orexin-A and -B, and ghrelin are potent orexigenic peptides. The effects of ACT462206, a novel dual orexin receptor antagonist (DORA), on ghrelin-induced feeding were examined in adult male Wistar rats. Hyperphagia induced by the intracerebroventricular (icv) administration of ghrelin was significantly suppressed for at least 2 h by pretreatment with icv administration of DORA. A marked increase was observed in the number of neurons showing Fos immunoreactivity in the paraventricular nucleus, arcuate nucleus and lateral hypothalamic area (LHA), 90 min after icv administration of ghrelin...
January 4, 2017: Journal of Physiological Sciences: JPS
https://www.readbyqxmd.com/read/28051300/design-and-synthesis-of-potent-and-highly-selective-orexin-1-receptor-antagonists-with-a-morphinan-skeleton-and-their-pharmacologies
#12
Hiroshi Nagase, Naoshi Yamamoto, Masahiro Yata, Sayaka Ohrui, Takahiro Okada, Tsuyoshi Saitoh, Noriki Kutsumura, Yasuyuki Nagumo, Yoko Irukayama-Tomobe, Yukiko Ishikawa, Yasuhiro Ogawa, Shigeto Hirayama, Daisuke Kuroda, Yurie Watanabe, Hiroaki Gouda, Masashi Yanagisawa
Nalfurafine, a κ-selective opioid receptor agonist, unexpectedly showed a selective antagonist activity toward the orexin 1 receptor (OX1R) (Ki = 250 nM). Modification of the 17-amino side chain of the opioid ligand to an arylsulfonyl group and the 6-furan acrylamide chain to 2-pyridyl acrylamide led to compound 71 with improvement of the antagonist activity (OX1R, Ki = 1.36 nM; OX2R, not active) without any detectable affinity for the opioid receptor. The dihydrosulfate salt of 71, freely soluble in water, attenuated the physical dependence of morphine...
January 18, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28041630/the-analgesic-effect-of-orexin-a-in-a-murine-model-of-chemotherapy-induced-neuropathic-pain
#13
Satoshi Toyama, Naohito Shimoyama, Megumi Shimoyama
Orexins are neuropeptides that are localized to neurons in the lateral and dorsal hypothalamus but its receptors are distributed to many different regions of the central nervous system. Orexins are implicated in a variety of physiological functions including sleep regulation, energy homeostats, and stress reactions. Furthermore, orexins administered exogenously have been shown to have analgesic effects in animal models. A type of intractable pain in patients is pain due to chemotherapy-induced peripheral neuropathy (CIPN)...
December 24, 2016: Neuropeptides
https://www.readbyqxmd.com/read/28039192/orexin-signaling-in-rostral-lateral-hypothalamus-and-nucleus-accumbens-shell-in-the-control-of-spontaneous-physical-activity-in-high-and-low-activity-rats
#14
Claudio Esteban Perez-Leighton, Morgan R Little, Martha K Grace, Charles J Billington, Catherine M Kotz
Spontaneous physical activity (SPA) describes activity outside of formal exercise and shows large inter-individual variability. The hypothalamic orexin/hypocretin peptides are key regulators of SPA. Orexins drive SPA within multiple brain sites, including rostral lateral hypothalamus (LH) and nucleus accumbens shell (NAcSh). Rats with high basal SPA (high activity, HA) show higher orexin mRNA expression and SPA after injection of orexin-A in rostral LH compared to low activity (LA) rats. Here we explored the contribution of orexin signaling in rostral LH and NAcSh to the HA/LA phenotype...
December 30, 2016: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28035899/peripherally-administered-orexin-improves-survival-of-mice-with-endotoxin-shock
#15
Yasuhiro Ogawa, Yoko Irukayama-Tomobe, Nobuyuki Murakoshi, Maiko Kiyama, Yui Ishikawa, Naoto Hosokawa, Hiromu Tominaga, Shuntaro Uchida, Saki Kimura, Mika Kanuka, Miho Morita, Michito Hamada, Satoru Takahashi, Yu Hayashi, Masashi Yanagisawa
Sepsis is a systemic inflammatory response to infection, accounting for the most common cause of death in intensive care units. Here, we report that peripheral administration of the hypothalamic neuropeptide orexin improves the survival of mice with lipopolysaccharide (LPS) induced endotoxin shock, a well-studied septic shock model. The effect is accompanied by a suppression of excessive cytokine production and an increase of catecholamines and corticosterone. We found that peripherally administered orexin penetrates the blood-brain barrier under endotoxin shock, and that central administration of orexin also suppresses the cytokine production and improves the survival, indicating orexin's direct action in the central nervous system (CNS)...
December 30, 2016: ELife
https://www.readbyqxmd.com/read/28035181/functional-connectivity-of-basolateral-amygdala-neurons-carrying-orexin-receptors-and-melanin-concentrating-hormone-receptors-in-regulating-sociability-and-mood-related-behaviors
#16
Tae-Kyung Kim, Pyung-Lim Han
Chronic stress induces changes in neuronal functions in specific brain regions regulating sociability and mood-related behaviors. Recently we reported that stress-induced persistent upregulation of the neuropeptides orexin and melanin-concentrating hormone (MCH) in the basolateral amygdala (BLA) and the resulting activation of orexin receptors or MCH receptors within the BLA produced deficits in sociability and mood-related behaviors. In the present study, we investigated the neural targets that were innervated by BLA neurons containing orexin receptors or MCH receptors...
December 2016: Experimental Neurobiology
https://www.readbyqxmd.com/read/28035034/identification-of-suvorexant-in-urine-using-liquid-chromatography-quadrupole-time-of-flight-mass-spectrometry-lc-q-tof-ms
#17
Sydney Sullinger, Kelsie Bryand, Sarah Kerrigan
Suvorexant (Belsomra(®)) is a new hypnotic drug with a novel mechanism of action. In prescribed doses of 10 mg before bedtime, the drug produces rapid onset of sleep by inhibiting the orexin neurons of the arousal system, promoting decreased wakefulness. Suvorexant is a potent and highly selective dual orexin receptor antagonist. Sedative hypnotics are of forensic importance due to their widespread use, potential for additive effects with other central nervous system depressants, impairing effects and potential for misuse...
December 29, 2016: Journal of Analytical Toxicology
https://www.readbyqxmd.com/read/28025809/the-human-orexin-hypocretin-receptor-crystal-structures
#18
Jie Yin, Daniel M Rosenbaum
The human orexin/hypocretin receptors (hOX1R and hOX2R) are G protein-coupled receptors (GPCRs) that mediate the diverse functions of the orexin/hypocretin neuropeptides. Orexins/hypocretins produced by neurons in the lateral hypothalamus stimulate their cognate GPCRs in multiple regions of the central nervous system to control sleep and arousal, circadian rhythms, metabolism, reward pathways, and other behaviors. Dysfunction of orexin/hypocretin signaling is associated with human disease, and the receptors are active targets in a number of therapeutic areas...
December 27, 2016: Current Topics in Behavioral Neurosciences
https://www.readbyqxmd.com/read/28025575/patterned-feeding-induces-neuroendocrine-behavioral-and-genetic-changes-that-promote-palatable-food-intake
#19
S Sirohi, A Van Cleef, J F Davis
BACKGROUND: Selection of a healthy diet is the cornerstone for treating obesity and metabolic disease. Unfortunately, the majority of diets fail leading to weight regain and in some cases, pathological feeding behavior. We hypothesize that alternating bouts of caloric overconsumption and caloric restriction, behavioral manifestations of dieting, induce neuroendocrine, behavioral, and genetic changes that promote future bouts of palatable food intake. METHODS: To test this hypothesis, we subjected male Long Evans rats to a HFD feeding paradigm that induced a pattern of caloric overconsumption and caloric restriction...
December 27, 2016: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28012092/the-hypocretin-orexin-neuronal-networks-in-zebrafish
#20
Idan Elbaz, Talia Levitas-Djerbi, Lior Appelbaum
The hypothalamic Hypocretin/Orexin (Hcrt) neurons secrete two Hcrt neuropeptides. These neurons and peptides play a major role in the regulation of feeding, sleep wake cycle, reward-seeking, addiction, and stress. Loss of Hcrt neurons causes the sleep disorder narcolepsy. The zebrafish has become an attractive model to study the Hcrt neuronal network because it is a transparent vertebrate that enables simple genetic manipulation, imaging of the structure and function of neuronal circuits in live animals, and high-throughput monitoring of behavioral performance during both day and night...
December 24, 2016: Current Topics in Behavioral Neurosciences
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