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https://www.readbyqxmd.com/read/28727208/differential-expression-of-appetite-regulating-genes-in-avian-models-of-anorexia-and-obesity
#1
Jiaqing Yi, Jingwei Yuan, Elizabeth R Gilbert, Paul B Siegel, Mark A Cline
Chickens from lines that have been selected for low (LWS) or high (HWS) juvenile body weight for more than 57 generations provide a unique model to research appetite regulation. The LWS display different severities of anorexia while all HWS become obese. Herein we measured mRNA abundance of various factors in appetite-associated nuclei in the hypothalamus. The lateral hypothalamus (LHA), paraventricular nucleus (PVN), ventromedial hypothalamus (VMH), dorsomedial nucleus (DMN), and arcuate nucleus (ARC) were collected from 5 day-old chicks that were fasted for 180 minutes or provided continuous access to food...
July 20, 2017: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/28717967/orexin-a-hypocretin-modulates-leptin-receptor-mediated-signaling-by-allosteric-modulations-mediated-by-the-ghrelin-ghs-r1a-receptor-in-hypothalamic-neurons
#2
Mireia Medrano, David Aguinaga, Irene Reyes-Resina, Enric I Canela, Josefa Mallol, Gemma Navarro, Rafael Franco
The hypothalamus is a key integrator of nutrient-seeking signals in the form of hormones and metabolites originated in both the central nervous system and the periphery. The main autocrine and paracrine target of orexinergic-related hormones such as leptin, orexin/hypocretin, and ghrelin are neuropeptide Y neurons located in the arcuate nucleus of the hypothalamus. The aim of this study was to investigate the expression and the molecular and functional relationships between leptin, orexin/hypocretin and ghrelin receptors...
July 17, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28709906/effects-of-feeding-time-on-daily-rhythms-of-neuropeptide-and-clock-gene-expression-in-the-rat-hypothalamus
#3
Dawei Wang, Anne-Loes Opperhuizen, Jane Reznick, Nigel Turner, Yan Su, Gregory J Cooney, Andries Kalsbeek
Shiftworkers are exposed to several adverse health conditions, one being eating at night. Food consumption at an unnatural time-of-day is thought to be one of the main factors responsible for the increased risk of developing metabolic diseases, such as obesity and diabetes mellitus. The underlying mechanism is considered to include disruption of the circadian organization of physiology, leading to disruption of metabolism. When food is consumed at night, the hypothalamus, a brain region central to homeostasis, receives contradicting input from the central clock and the systemic circulation...
July 11, 2017: Brain Research
https://www.readbyqxmd.com/read/28707143/clinical-sleep-wake-disorders-ii-focus-on-insomnia-and-circadian-rhythm-sleep-disorders
#4
Kai Spiegelhalder, Christoph Nissen, Dieter Riemann
Insomnia and circadian rhythm sleep disorders affect large proportions of the population and have pronounced effects on quality of life and daytime performance. While the neurobiology of insomnia is not yet fully understood, circadian rhythm sleep disorders are assumed to be caused by a mismatch between the individual circadian phase position and the desired sleep-wake schedule. Benzodiazepines and non-benzodiazepine positive allosteric GABAA receptor modulators improve sleep onset and maintenance in the short-term treatment of insomnia...
July 14, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28705440/inhibition-of-trkb-at-the-nucleus-accumbens-using-ana-12-regulates-basal-and-stress-induced-orexin-a-expression-within-the-mesolimbic-system-and-affects-anxiety-sociability-and-motivation
#5
Idu Azogu, Helene Plamondon
Repeated stress exposure can lead to the development of anxiety and mood disorders. An emerging biological substrate of depression and associated pathology is the nucleus accumbens (NAc), which through interactions with limbic, cognitive and motor circuits can regulate a variety of stress responses. Within these circuits, orexin neurons are involved in arousal and stress adaptability, effects proposed mediated via brain-derived neurotrophic factor signaling. This study tested the hypotheses that 1) repeated exposure to heterotypic stress alters social ability and preference and passive avoidant behaviors, 2) TrkB receptors at the NAc shell regulates stress-induced behavioral responses and orexin expression within the mesocorticolimbic system...
July 10, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28701075/the-effect-of-orexin-a-on-motor-and-cognitive-functions-in-a-rat-model-of-parkinson-s-disease
#6
Zahra Hadadianpour, Farangis Fatehi, Fateme Ayoobi, Ayat Kaeidi, Ali Shamsizadeh, Iman Fatemi
OBJECTIVE:  The aim of this study was to evaluate the effect of orexin-A (OX-A) and the orexin-1 receptor antagonist SB-334867 (SB) on motor and cognitive functions in a rat model of Parkinson's disease. METHODS: Parkinson was induced by intracerebroventricular (i.c.v) injection of 6- hydroxydopamine (6-OHDA) (200 μg/rat). 72 h later, the treatment was initiated by i.c.v administration of SB (30 nmol/rat) and/or OX-A (0.3 nmol/rat) for 10 days. Motor functions were monitored using rotarod and hanging tests...
July 12, 2017: Neurological Research
https://www.readbyqxmd.com/read/28696162/physiological-and-brain-alterations-produced-by-high-fat-diet-in-male-and-female-rats-can-be-modulated-by-increased-levels-of-estradiol-during-critical-periods-of-development
#7
Beatriz Carrillo, Paloma Collado, Francisca Díaz, Julie A Chowen, Mª Ángeles Pérez-Izquierdo, Helena Pinos
BACKGROUND: Overnutrition due to a high-fat diet (HFD) can increase the vulnerability of the metabolic system to maladjustments. Estradiol has an inhibitory role on food intake and this hormone has demonstrated to be a crucial organizer during brain development. OBJECTIVE: Our aim was to determine whether increased levels of estradiol in the early postnatal period modulate the alterations in metabolism and brain metabolic circuits produced by overnutrition. METHODS: Twenty-four male and 24 female Wistar rats were submitted to a HFD (34...
July 11, 2017: Nutritional Neuroscience
https://www.readbyqxmd.com/read/28690152/decreased-expression-of-orexin-1-receptor-in-adult-mice-testes-during-alloxan-induced-diabetes-mellitus-perturbs-testicular-steroidogenesis-and-glucose-homeostasis
#8
Deepanshu Joshi, Debarshi Sarkar, Shio Kumar Singh
Diabetes mellitus (DM) affects male reproductive system and causes infertility. The male reproductive health is largely dependent upon uptake and proper utilization of glucose by testicular cells. Results show involvement of orexin A (OXA) and its receptor (OX1R) in regulation of steroidogenesis and glucose homeostasis in adult mice testis. However, the role of OX1R in regulation of testicular functions during hyperglycemia has not been investigated so far. The present study, therefore, examined the role of OX1R in regulation of steroidogenesis and glucose homeostasis in testis of adult mice during alloxan-induced type 1 DM...
July 6, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28680929/orexins-and-the-cardiovascular-events-of-awakening
#9
REVIEW
Alessandro Silvani
This brief review aims to provide an updated account of the cardiovascular events of awakening, proposing a testable conceptual framework that links these events with the neural control of sleep and the autonomic nervous system, with focus on the hypothalamic orexin (hypocretin) neurons. Awakening from non-rapid-eye-movement sleep entails coordinated changes in brain and cardiovascular activity: the neural "flip-flop" switch that governs state transitions becomes biased toward the ascending arousal systems, arterial blood pressure and heart rate rise toward waking values, and distal skin temperature falls...
2017: Temperature: Multidisciplinary Biomedical Journal
https://www.readbyqxmd.com/read/28674442/investigating-the-effects-of-orexin-a-on-thermogenesis-in-human-deep-neck-brown-adipose-tissue
#10
M F Pino, A Divoux, A V Simmonds, S R Smith, L M Sparks
BACKGROUND: Despite successful pre-clinical testing, 85% of early clinical trials for novel drugs fail. Most futilities originate from molecular mechanisms of the drug(s) tested. It is critically important to develop validated human cell-based model systems in which animal-based research can be translated in order to complement the preclinical in vivo findings prior to implementation of a clinical trial. Obesity is associated with reduced circulating levels of Orexin-A (OX-A) in humans...
July 4, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28671376/insomnia-pharmacologic-therapy
#11
Eric Matheson, Barry L Hainer
Insomnia accounts for more than 5.5 million visits to family physicians each year. Although behavioral interventions are the mainstay of treatment, pharmacologic therapy may be necessary for some patients. Understanding the risks and benefits of insomnia medications is critical. Controlled-release melatonin and doxepin are recommended as first-line agents in older adults; the so-called z-drugs (zolpidem, eszopiclone, and zaleplon) should be reserved for use if the first-line agents are ineffective. For the general population with difficulty falling asleep, controlled-release melatonin and the z-drugs can be considered...
July 1, 2017: American Family Physician
https://www.readbyqxmd.com/read/28669028/the-excitatory-inhibitory-input-to-orexin-hypocretin-neuron-soma-undergoes-day-night-reorganization
#12
Claudia Laperchia, Roberta Imperatore, Idris A Azeez, Federico Del Gallo, Giuseppe Bertini, Gigliola Grassi-Zucconi, Luigia Cristino, Marina Bentivoglio
Orexin (OX)/hypocretin-containing neurons are main regulators of wakefulness stability, arousal, and energy homeostasis. Their activity varies in relation to the animal's behavioral state. We here tested whether such variation is subserved by synaptic plasticity phenomena in basal conditions. Mice were sacrificed during day or night, at times when sleep or wake, respectively, predominates, as assessed by electroencephalography in matched mice. Triple immunofluorescence was used to visualize OX-A perikarya and varicosities containing the vesicular glutamate transporter (VGluT)2 or the vesicular GABA transporter (VGAT) combined with synaptophysin (Syn) as a presynaptic marker...
July 1, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/28667055/increased-activity-of-the-orexin-system-in-the-paraventricular-nucleus-contributes-to-salt-sensitive-hypertension
#13
Michael J Huber, Yuanyuan Fan, Enshe Jiang, Fengli Zhu, Robert A Larson, Jianqun Yan, Ningjun Li, Qing-Hui Chen, Zhiying Shan
The orexin system is involved in vasopressin (AVP) regulation and its over activation has been implicated in hypertension. However, its role in salt-sensitive hypertension (SSHTN) is unknown. Here we test the hypothesis that hyperactivity of the orexin system in the paraventricular nucleus (PVN) contributes to SSHTN via enhancing AVP signaling. Eight-week-old male Dahl salt sensitive (Dahl S) and age and sex matched Sprague Dawley (SD) rats were placed on a high salt (HS, 8% NaCl) or normal salt (NS, 0.4% NaCl) diet for 4 weeks...
June 30, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28666854/small-interfering-rna-mediated-knockdown-of-irisin-suppresses-food-intake-and-modulates-appetite-regulatory-peptides-in-zebrafish
#14
Lakshminarasimhan Sundarrajan, Suraj Unniappan
Irisin is a myokine encoded in fibronectin type III domain containing 5 (FNDC5). FNDC5 forms an integral part of the muscle post-exercise, and causes an increase in energy expenditure in mammals. Irisin is abundantly expressed in cardiac and skeletal muscles and is secreted upon activation of peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1 alpha). Irisin regulates feeding behaviour and cardiovascular function in mammals. More recently, irisin has gained importance as a potential biomarker for myocardial infarction due to its abundance in cardiac muscle...
June 27, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28663311/the-use-of-physiology-based-pk-and-pd-modeling-in-the-discovery-of-the-dual-orexin-receptor-antagonist-act-541468
#15
Alexander Treiber, Ruben de Kanter, Catherine Roch, John Gatfield, Christoph Boss, Markus von Raumer, Benno Schindelholz, Clemens Muehlan, Joop van Gerven, Francois Jenck
The identification of new sleep drugs poses particular challenges in drug discovery due to disease-specific requirements such as rapid onset of action, sleep maintenance throughout major parts of the night, and absence of residual next-day effects. Robust tools to estimate drug levels in human brain are therefore key for a successful discovery program. Animal models constitute an appropriate choice for drugs without species differences in receptor pharmacology or pharmacokinetics. Translation to man becomes more challenging in case inter-species differences are prominent...
June 29, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28663114/palatable-food-self-administration-and-reinstatement-are-not-affected-by-dual-orexin-receptor-antagonism
#16
Shaun Yon-Seng Khoo, Kelly J Clemens, Gavan P McNally
The orexins are widely regarded potential therapeutic targets for a range of disorders of appetitive motivation, including obesity. The motivational activator theory, the first coherent account of the orexin system's role in appetitive motivation, predicts that orexin release motivates appetitive behaviour when the reinforcer is highly salient, available under a high unit-cost or when reward seeking is cue-driven. The present study tested the effect of intracerebroventricular (i.c.v.) administration of the highly potent and commercially available dual orexin receptor antagonist, TCS 1102, on self-administration and reinstatement of palatable food seeking in hungry and sated rats...
June 26, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28652355/neural-mechanism-for-hypothalamic-mediated-autonomic-responses-to-light-during-migraine
#17
Rodrigo Noseda, Alice J Lee, Rony-Reuven Nir, Carolyn A Bernstein, Vanessa M Kainz, Suzanne M Bertisch, Catherine Buettner, David Borsook, Rami Burstein
Migraineurs avoid light because it intensifies their headache. However, this is not the only reason for their aversion to light. Studying migraineurs and control subjects, we found that lights triggered more changes in autonomic functions and negative emotions during, rather than in the absence of, migraine or in control subjects, and that the association between light and positive emotions was stronger in control subjects than migraineurs. Seeking to define a neuroanatomical substrate for these findings, we showed that, in rats, axons of retinal ganglion cells converge on hypothalamic neurons that project directly to nuclei in the brainstem and spinal cord that regulate parasympathetic and sympathetic functions and contain dopamine, histamine, orexin, melanin-concentrating hormone, oxytocin, and vasopressin...
June 26, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28651750/reduced-orexin-immunoreactivity-in-perry-syndrome-and-multiple-system-atrophy
#18
Takayasu Mishima, Koji Kasanuki, Shunsuke Koga, Monica Castanedes-Casey, Zbigniew K Wszolek, Yoshio Tsuboi, Dennis W Dickson
INTRODUCTION: Orexin is a neuropeptide that plays a key role in maintaining a state of arousal, and possibly associates with sleep apnea syndrome (SAS). Reduced orexin immunoreactivity has been reported in various neurologic conditions such as narcolepsy, Alzheimer's disease, Lewy body disease and multiple system atrophy (MSA); however, there has been no report investigating orexin in Perry syndrome, a rare hereditary neurodegenerative disease characterized by four clinical cardinal signs (parkinsonism, depression/apathy, weight loss, and central hypoventilation)...
June 12, 2017: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/28649201/evaluation-of-jnj-54717793-a-novel-brain-penetrant-selective-orexin-1-receptor-antagonist-in-two-rat-models-of-panic-attack-provocation
#19
Pascal Bonaventure, Christine Dugovic, Brock Shireman, Cathy Preville, Sujin Yun, Brian Lord, Diane Nepomuceno, Michelle Wennerholm, Timothy Lovenberg, Nicolas Carruthers, Stephanie D Fitz, Anantha Shekhar, Philip L Johnson
Orexin neurons originating in the perifornical and lateral hypothalamic area are highly reactive to anxiogenic stimuli and have strong projections to anxiety and panic-associated circuitry. Recent studies support a role for the orexin system and in particular the orexin 1 receptor (OX1R) in coordinating an integrative stress response. However, no selective OX1R antagonist has been systematically tested in two preclinical models of using panicogenic stimuli that induce panic attack in the majority of people with panic disorder, namely an acute hypercapnia-panic provocation model and a model involving chronic inhibition of GABA synthesis in the perifornical hypothalamic area followed by intravenous sodium lactate infusion...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28642284/excitation-of-gabaergic-neurons-in-the-bed-nucleus-of-the-stria-terminalis-triggers-immediate-transition-from-non-rapid-eye-movement-sleep-to-wakefulness-in-mice
#20
Shota Kodani, Shingo Soya, Takeshi Sakurai
Emotionally salient situations usually trigger arousal along with autonomic and neuroendocrine reactions. To examine whether the extended amygdala plays a role in sleep/wakefulness regulation, we examined the effects of optogenetic and pharmacogenetic excitation of GABAergic neurons in the bed nucleus of the stria terminalis (GABA(BNST) neurons). Acute optogenetic excitation of these cells during non-rapid eye movement (NREM) sleep resulted in immediate state transition to wakefulness, while stimulation during rapid eye movement (REM) sleep showed no effect on sleep/wakefulness states in male mice...
June 22, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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