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https://www.readbyqxmd.com/read/29138106/the-subthalamic-neurons-are-activated-by-both-orexin-a-and-orexin-b
#1
Qing Sheng, Yan Xue, Ying Wang, An-Qi Chen, Cui Liu, Yun-Hai Liu, Hong-Yan Chu, Lei Chen
The subthalamic nucleus is an important nucleus in the indirect pathway of the basal ganglia circuit and therefore is involved in motor control under both normal and pathological conditions. Morphological studies reveal that the subthalamic nucleus receives relatively dense orexinergic projections originating from the hypothalamus. Both orexin-1 (OX1) and orexin-2 (OX2) receptors are expressed in the subthalamic nucleus. To explore the functions of orexinergic system in the subthalamic nucleus, extracellular electrophysiological recordings and behavioral tests were performed in the present study...
November 11, 2017: Neuroscience
https://www.readbyqxmd.com/read/29129052/synthesis-and-evaluation-of-orexin-1-receptor-antagonists-with-improved-solubility-and-cns-permeability
#2
David A Perrey, Ann M Decker, Yanan Zhang
Orexins are hypothalamic neuropeptides playing important roles in many functions including the motivation of addictive behaviors. Blockade of the orexin-1 receptor has been suggested as a potential strategy for the treatment of drug addiction. We have previously reported OX1 receptor antagonists based on the tetrahydroisoquinoline scaffold with excellent OX1 potency and selectivity; however, these compounds had high lipophilicity (clogP > 5) and low to moderate solubility. In an effort to improve their properties, we have designed and synthesized a series of analogues where the 7-position substituents known to favor OX1 potency and selectivity were retained, and groups of different nature were introduced at the 1-position where substitution was generally tolerated as demonstrated in previous studies...
November 20, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29079898/overexpression-of-a-predominantly-root-expressed-nac-transcription-factor-in-wheat-roots-enhances-root-length-biomass-and-drought-tolerance
#3
Dandan Chen, Shoucheng Chai, C Lynne McIntyre, Gang-Ping Xue
TaRNAC1 is a constitutively and predominantly root-expressed NAC transcription factor. TaRNAC1 overexpression in wheat roots confers increased root length, biomass and drought tolerance and improved grain yield under water limitation. A large and deep root system is an important trait for yield sustainability of dryland cereal crops in drought-prone environments. This study investigated the role of a predominantly root-expressed NAC transcription factor from wheat (TaRNAC1) in the root growth. Expression analysis showed that TaRNAC1 was a constitutively expressed gene with high level expression in the roots and was not drought-upregulated...
October 27, 2017: Plant Cell Reports
https://www.readbyqxmd.com/read/29066961/different-molecular-behavioral-endophenotypes-in-c57bl-6j-mice-predict-the-impact-of-ox1-receptor-blockade-on-binge-like-ethanol-intake
#4
Manuel Alcaraz-Iborra, Francisco Navarrete, Elisa Rodríguez-Ortega, Leticia de la Fuente, Jorge Manzanares, Inmaculada Cubero
Ethanol (EtOH) research has focused on stages of dependence. It is of paramount importance to more deeply understand the neurobehavioral factors promoting increased risk for EtOH binge drinking during the early stages of the addiction cycle. The first objective of this study was to evaluate whether C57BL/6J mice showing high drinking in the dark (DID) exhibit neurobehavioral traits known to contribute to EtOH binge-drinking disorders. Comparing high vs. low drinkers (HD/LD), we evaluated different types of basal anxiety-like responses, EtOH preference and sensitivity to the reinforcing properties of EtOH, and basal mRNA expression of the OX1/OX2 receptors (OX1r/OX2r) within the prefrontal cortex (PFC) and the nucleus accumbens (NAcc)...
2017: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/29042364/a-cd200r-cd28-fusion-protein-appropriates-an-inhibitory-signal-to-enhance-t-cell-function-and-therapy-of-murine-leukemia
#5
Shannon K Oda, Andrew W Daman, Nicolas M Garcia, Felecia Wagener, Thomas M Schmitt, Xiaoxia Tan, Aude G Chapuis, Philip D Greenberg
Acute myeloid leukemia (AML), the most common adult acute leukemia in the U.S., has the poorest survival rate, with 26% of patients surviving 5 years. Adoptive immunotherapy with T cells genetically modified to recognize tumors is a promising and evolving treatment option. However, antitumor activity, particularly in the context of progressive leukemia, can be dampened both by limited costimulation and triggering of immunoregulatory checkpoints that attenuate T cell responses. Expression of CD200 (OX2), a negative regulator of T cell function that binds CD200R, is commonly increased in leukemia and other malignancies, and is associated with poor prognosis in leukemia patients...
October 17, 2017: Blood
https://www.readbyqxmd.com/read/29042271/blockade-of-the-orexin-receptors-in-the-ca1-region-of-hippocampus-decreased-the-lateral-hypothalamic-induced-antinociceptive-responses-in-the-model-of-orofacial-formalin-test-in-the-rats
#6
Amir Haghparast, Iman Shafiei, Amir-Mohammad Alizadeh, Somayeh Ezzatpanah, Abbas Haghparast
The role of hippocampus and lateral hypothalamus (LH) in modulation of formalin-induced nociception has been established. The present study aims to examine the role of orexin receptors in the Cornu Ammonis 1 (CA1) region of hippocampus in modulation of the LH-induced antinociception in the orofacial formalin test. Male Wistar rats were unilaterally implanted with two cannulae into the LH and CA1. Intra-LH microinjection of carbachol was done 5min after intra-CA1 administration of SB-334867 (OX1R antagonist) or TCS OX2 29 (OX2R antagonist)...
October 14, 2017: Peptides
https://www.readbyqxmd.com/read/28993579/role-of-orexin-receptor-subtypes-in-the-inhibitory-effects-of-orexin-a-on-potassium-chloride-induced-increases-in-intracellular-calcium-ion-levels-in-neurons-derived-from-dorsal-root-ganglion-of-carrageenan-treated-rats
#7
Manabu Ishikawa, Yuri Aono, Tadashi Saigusa
We analysed the roles of orexin receptors in the effects of orexin-A on KCl-induced increases in intracellular calcium ion levels ([Ca(2+)]i) in C-fiber-like small neurons of rats with inflammation induced by intraplantar injection of carrageenan into the hind paw. Controls were treated with saline. Paw withdrawal and threshold forces in response to tactile stimuli were determined using von Frey filaments. [Ca(2+)]i in C-fiber-like neurons derived from dorsal root ganglia was visualised using a calcium fluorescence probe...
October 6, 2017: Journal of Oral Science
https://www.readbyqxmd.com/read/28928300/zoonotic-surveillance-for-rickettsiae-in-rodents-and-mapping-of-vectors-of-rickettsial-diseases-in-india-a-multi-centric-study
#8
Rina Tilak, Rajesh Kunwar, P K Tyagi, Anurag Khera, R K Joshi, Urmila B Wankhade
BACKGROUND: The global resurgence of rickettsial diseases and their potential to impact the fitness of military personnel and inflict widespread casualties amongst civil populations has emerged as a major cause of public health concern. Absence of surveillance system, lack of awareness amongst medical fraternity to rickettsial activity along with the difficulty in diagnosis because of their protean clinical manifestations are reasons for the outbreaks of these diseases. OBJECTIVES: To determine rickettsial activity amongst rodents and study vector diversity, abundance and their distribution to enable mapping of rickettsial hotspots...
July 2017: Indian Journal of Public Health
https://www.readbyqxmd.com/read/28890208/role-of-orexin-receptors-in-the-ventral-tegmental-area-on-acquisition-and-expression-of-morphine-induced-conditioned-place-preference-in-the-rats
#9
Sharareh Farahimanesh, Shahram Zarrabian, Abbas Haghparast
The orexins are hypothalamic neuropeptides and their role in reward processing and drug addiction has been demonstrated. The extent of involvement of each orexin receptor in the acquisition and expression of conditioned place preference (CPP) for morphine is still a matter of controversy. We investigated the functional differences between orexin-1 and -2 receptor blockade in the ventral tegmental area (VTA) on the acquisition and expression of morphine CPP. A total of 86 adult male Wistar rats weighing 250±30g (age 7-8weeks) received intra-VTA microinjection of either SB334867 (0...
September 4, 2017: Neuropeptides
https://www.readbyqxmd.com/read/28889006/role-of-intra-accumbal-orexin-receptors-in-the-acquisition-of-morphine-induced-conditioned-place-preference-in-the-rats
#10
Mirmohammadali Mirramezani Alizamini, Zahra Farzinpour, Somayeh Ezzatpanah, Abbas Haghparast
Orexin receptor shave essential role in the induction of reward-related behaviors to several drugs of abuse. In the present study, we investigated the effects of bilateral administration of SB334867, as an orexin-1 receptor antagonist, and TCS OX2 29, as an orexin-2 receptor antagonist, into the nucleus accumbens (NAc) on the acquisition of morphine-induced conditioned place preference (CPP) in the rats. Adult male Wistar rats (n=80; 220-250g) were entered in a CPP paradigm. Bilateral microinjections of different doses of SB334867 (1, 3, 10 and 30nM) or TCS OX2 29 (3, 10, 30 and 100nM) into the NAc (0...
November 1, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28866050/orexin-receptors-mediate-long-term-depression-of-excitatory-synaptic-transmission-in-the-spinal-cord-dorsal-horn
#11
Ki Bum Park, Haein Weon
Neuropeptides orexin-A and -B are related to the regulation of sleep/wakefulness and feeding behaviors. Recently, the peptides have also been shown to yield antinociceptive effects in various pain models. However, it is not clear whether orexins are involved in forms of synaptic plasticity, such as long-term potentiation (LTP) and long-term depression (LTD), the increase and the decrease of synaptic efficacy, respectively. In the present study, we examined whether orexin receptor type 1 (OX1) and 2 (OX2) are involved in the induction or maintenance of LTD of excitatory synaptic transmission using transverse spinal cord slices of young rats...
November 1, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28831734/interactions-of-hallucinogens-with-the-glutamatergic-system-permissive-network-effects-mediated-through-cortical-layer-v-pyramidal-neurons
#12
Gerard J Marek
Recordings made from layer V (L5) pyramidal cells of the prefrontal cortex (PFC) and neocortex in rodent slice preparations have shown that serotonin (5-hydroxytryptamine, 5-HT) and serotonergic hallucinogens induce an increase in the frequency of spontaneous excitatory postsynaptic currents (EPSCs) in the apical dendritic field by activating 5-HT2A receptors. Serotonergic hallucinogens induce late EPSCs and increase recurrent network activity when subcortical or mid-cortical regions are stimulated at low frequencies (e...
August 23, 2017: Current Topics in Behavioral Neurosciences
https://www.readbyqxmd.com/read/28799301/rickettsial-infections-in-goa-not-just-scrub-typhus
#13
Kedareshwar Narvencar, Gurleen Kaur, Savio Rodrigues
BACKGROUND AND OBJECTIVE: Rickettsial infections are an important cause of undifferentiated febrile illness in tropics. While scrub typhus was reported from Goa, other rickettsial infections have not been reported earlier. The present study was planned to identify pattern of rickettsial infections in Goa. MATERIALS AND METHODS: All patients presenting with undiagnosed acute febrile illness were recruited over a two-year period. Other causes of febrile illness were ruled out by appropriate tests...
August 2017: Journal of the Association of Physicians of India
https://www.readbyqxmd.com/read/28794459/multiple-excitatory-actions-of-orexins-upon-thalamo-cortical-neurons-in-dorsal-lateral-geniculate-nucleus-implications-for-vision-modulation-by-arousal
#14
Lukasz Chrobok, Katarzyna Palus-Chramiec, Anna Chrzanowska, Mariusz Kepczynski, Marian Henryk Lewandowski
The orexinergic system of the lateral hypothalamus plays a crucial role in maintaining wakefulness and mediating arousal in a circadian time-dependent manner. Due to the extensive connections of orexinergic neurons, both orexins (OXA and OXB) exert mainly excitatory effects upon remote brain areas, including the thalamus. The dorsal lateral geniculate nucleus (DLG) is a relay thalamic centre for the visual system. Its thalamo-cortical (TC) neurons convey photic information from the retina to the primary visual cortex...
August 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28741623/effects-of-suvorexant-a-dual-orexin-hypocretin-receptor-antagonist-on-impulsive-behavior-associated-with-cocaine
#15
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/28663311/the-use-of-physiology-based-pharmacokinetic-and-pharmacodynamic-modeling-in-the-discovery-of-the-dual-orexin-receptor-antagonist-act-541468
#16
RANDOMIZED CONTROLLED TRIAL
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 owing 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 when interspecies differences are prominent...
September 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28631980/orexin-research-patent-news-from-2016
#17
REVIEW
Christoph Boss, Catherine Roch
The orexin system consists of two G-protein-coupled receptors, orexin 1 and orexin 2 and two endogenous ligands, orexin A and orexin B . It is evolutionarily highly conserved. It is involved in the promotion of wakefulness as well as in anxiety and addictive disorders. In addition, its activation via the Ox1 receptor triggers apoptosis in several cancer cell lines. Dual orexin receptor antagonists are successfully used to treat primary insomnia. The major open questions are now related to the clinical validation of Ox1 selective antagonists...
October 2017: Expert Opinion on Therapeutic Patents
https://www.readbyqxmd.com/read/28609741/electrocatalytic-activity-of-manganese-oxide-nanosphere-immobilized-onto-deoxyribonucleic-acid-modified-electrode-application-to-determine-environmental-pollutant-thiourea-at-natural-ph
#18
Afshin Maleki, Hiua Daraei, Nader Amini
Based on immobilizing manganese oxide nanospheres (MnOxNsph)/deoxyribonucleic (DNA) on glassy carbon electrode (MnOxNsph/DNA/GCE), a new electrochemical biosensor for the detection of thiourea (TU) was fabricated. In order to prepare DNA template, cyclic voltammetry (CV) method was used. Scanning electron microscopy (SEM) was used for characterization of MnOx/DNA. Electrochemical impedance spectroscopy was utilized to confirm the successful stepwise assembly procedure of the biosensor. The electrocatalytical behaviors of the biosensor were also investigated by cyclic voltammetry and differential pulse voltammetry (DPV)...
June 7, 2017: Journal of Colloid and Interface Science
https://www.readbyqxmd.com/read/28575023/orexin-receptor-agonist-yan-7874-is-a-weak-agonist-of-orexin-hypocretin-receptors-and-shows-orexin-receptor-independent-cytotoxicity
#19
Ainoleena Turku, Maiju K Rinne, Gustav Boije Af Gennäs, Henri Xhaard, Dan Lindholm, Jyrki P Kukkonen
Two promising lead structures of small molecular orexin receptor agonist have been reported, but without detailed analyses of the pharmacological properties. One of them, 1-(3,4-dichlorophenyl)-2-[2-imino-3-(4-methylbenzyl)-2,3-dihydro-1H-benzo[d]imidazol-1-yl]ethan-1-ol (Yan 7874), is commercially available, and we set out to analyze its properties. As test system we utilized human OX1 and OX2 orexin receptor-expressing Chinese hamster ovary (CHO) K1 cells as well as control CHO-K1 and neuro-2a neuroblastoma cells...
2017: PloS One
https://www.readbyqxmd.com/read/28495313/posterior-hypothalamus-glutamate-infusion-decreases-pentylenetetrazol-induced-seizures-of-male-rats-through-hippocampal-histamine-increase
#20
Atieh Arzhang, Mahmoud Elahdadi Salmani, Taghi Lashkarbolouki, Iran Goudarzi
OBJECTIVES: Seizures are epileptic manifestations that are intrinsically modulated through different neurotransmitters and receptor systems. Although glutamate increases excitation and hence seizures, it activates other systems which could potentially terminate seizures. Histamine originates from neurons of the posterior hypothalamus (PH) and can mediate anticonvulsant properties, but the effect of local PH glutamate on hippocampal histamine content is unknown. Therefore, in this study, the effect of PH glutamate and the involvement of hippocampal histamine in pentylenetetrazol (PTZ) induced seizure activity was studied...
July 2017: Pharmacology, Biochemistry, and Behavior
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