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https://www.readbyqxmd.com/read/29348887/rna-seq-expression-profiling-of-rat-mcao-model-following-reperfusion-orexin-a
#1
Chun-Mei Wang, Yan-You Pan, Ming-Hui Liu, Bao-Hua Cheng, Bo Bai, Jing Chen
Orexin-A is a neuropeptide with potent neuroprotective activity towards cerebral ischemia-reperfusion (I/R) injury, but few studies have attempted to elucidate the mechanism. Herein, we performed global gene expression profiling of the hippocampus following reperfusion with Orexin-A using RNA sequencing (RNA-seq). RNA-seq identified 649 differentially expressed genes (DEGs) in the Orexin-A group compared with saline controls (I/R group), of which 149 were up-regulated and 500 were down-regulated. DEGs were confirmed using qRT-PCR, their molecular functions, biological processes and molecular components were explored using Gene Ontology (GO) analysis and 206 KEGG pathways were associated with Orexin-A treatment...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29338909/essential-structure-of-orexin-1-receptor-antagonist-ynt-707-part-ii-drastic-effect-of-the-14-hydroxy-group-on-the-orexin-1-receptor-antagonistic-activity
#2
Sayaka Ohrui, Naoshi Yamamoto, Tsuyoshi Saitoh, Noriki Kutsumura, Yasuyuki Nagumo, Yoko Irukayama-Tomobe, Yasuhiro Ogawa, Yukiko Ishikawa, Yurie Watanabe, Daichi Hayakawa, Hiroaki Gouda, Masashi Yanagisawa, Hiroshi Nagase
The 14-dehydration- and 14-H derivatives of the orexin 1 receptor (OX1R) antagonist YNT-707 (2) were synthesized. The obtained derivatives showed higher affinities for OX1R than the corresponding 14-hydroxy derivatives. The conformational analysis suggested that the 17-sulfonamide groups in the derivatives without the 14-hydroxy group have a greater tendency to be oriented toward the upper side of the D-ring compared with the 14-hydroxy derivatives. Additionally, the 14-dehydration-derivative with 6α-amide side chain showed significantly higher affinity than the 14-hydroxy derivative, while the corresponding 14-H derivative showed only slightly higher affinity...
December 30, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29325900/orexin-b-modulates-synaptic-transmission-of-rod-bipolar-cells-in-rat-retina
#3
Gong Zhang, Xiao-Hua Wu, Guo-Zhong Xu, Shi-Jun Weng, Xiong-Li Yang, Yong-Mei Zhong
Orexin-A, -B play a crucial role in arousal and feeding by activating two G-protein-coupled receptors: orexin receptor 1 (OX1R) and orexin receptor 2 (OX2R). Orexins, along with orexin receptors, are expressed in retinal neurons, and they have been shown to differentially modulate excitatory AMPA receptors of amacrine and ganglion cells in the inner retina. In this work we report that orexin-B modulates the activity of rod bipolar cells (RBCs) located in the outer retina of rat. Intravitreal injection of orexin-B increased the amplitude of the scotopic electroretinographic b-wave, a reflection of RBC activity, recorded in vivo...
January 8, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29325715/orexin-knockout-mice-exhibit-impaired-spatial-working-memory
#4
Ruozhi Dang, Qiuhan Chen, Jie Song, Chao He, Jun Zhang, Jianxia Xia, Zhian Hu
Orexins play a crucial role in the maintenance of arousal and are involved in the modulation of diverse physiological process, including cognitive function. Recent data have suggested that orexins are involved in learning and memory processes. The purpose of this study was to assess the effects of orexin deficiency on working memory. A delayed non-matching-to-place T-maze task was used to evaluate spatial working memory in mice lacking orexin prepro-peptide (orexin knockout; KO) and wild-type controls. We demonstrated that the number of correct choices in the orexin KO mice became lower than that of the controls over training...
January 8, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29315422/dietary-therapy-restores-glutamatergic-input-to-orexin-hypocretin-neurons-after-traumatic-brain-injury-in-mice
#5
Jonathan E Elliott, Samuel E De Luche, Madeline J Churchill, Cindy Moore, Akiva S Cohen, Charles K Meshul, Miranda M Lim
Study Objectives: In previous work, dietary branched chain amino acid (BCAA) supplementation, precursors to de novo glutamate and gamma-aminobutyric acid (GABA) synthesis, restored impaired sleep-wake regulation and orexin neuronal activity post-traumatic brain injury (TBI) in mice. TBI was speculated to reduce orexin neuronal activity through decreased regional excitatory (glutamate) and/or increased inhibitory (GABA) input. Therefore, we hypothesized TBI would decrease synaptic glutamate and/or increase synaptic GABA in nerve terminals contacting orexin neurons, and BCAA supplementation would restore TBI-induced changes in synaptic glutamate and/or GABA...
January 5, 2018: Sleep
https://www.readbyqxmd.com/read/29311142/regulation-of-lateral-hypothalamic-orexin-activity-by-local-gabaergic-neurons
#6
Loris L Ferrari, Daniel Park, Lin Zhu, Matthew R Palmer, Rebecca Y Broadhurst, Elda Arrigoni
Orexin (also known as hypocretin) neurons are considered a key component of the ascending arousal system. They are active during wakefulness, at which time they drive and maintain arousal, and are silent during sleep. Their activity is controlled by long-range inputs from many sources, as well as by more short-range inputs, including from presumptive GABAergic neurons in the lateral hypothalamus/perifornical region (LH/PF). To characterize local GABAergic input to orexin neurons we employed channelrhodopsin-2 (ChR2)-assisted-circuit-mapping in brain slices...
January 8, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29307079/functional-changes-of-orexinergic-reaction-to-psychoactive-substances
#7
REVIEW
Vincenzo Monda, Monica Salerno, Francesco Sessa, Renato Bernardini, Anna Valenzano, Gabriella Marsala, Christian Zammit, Roberto Avola, Marco Carotenuto, Giovanni Messina, Antonietta Messina
It is becoming increasingly apparent the importance of the central nervous system (CNS) as the major contributor to the regulation of systemic metabolism. Antipsychotic drugs are used often to treat several psychiatric disorders, including schizophrenia and bipolar disorder However, antipsychotic drugs prescription, particularly the second-generation ones (SGAs), such as clozapine and olanzapine, is related to a considerable weight gain which usually leads to obesity. The aim of this paper is to assess the influence of orexin A on sympathetic and hyperthermic reactions to several neuroleptic drugs...
January 6, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29303950/cns-drug-development-lessons-learned-part-4-the-role-of-brain-circuitry-and-genes-tasimelteon-as-an-example
#8
Sheldon H Preskorn
This is the fourth in a series of columns discussing the rational and targeted development of drugs to affect specific central nervous system (CNS) circuits in specific ways based on knowledge gained by molecular biology and the human genome project. The first column in this series described 6 CNS drugs with novel mechanisms of action developed over the last 25 years. The second column discussed differences between syndromic diagnoses as exemplified by the third through the fifth editions of the Diagnostic and Statistical Manual of Mental Disorders (DSM III through DSM-5) and the new approach to psychiatric diagnoses championed by the National Institute of Mental Health in their Research Domain Criteria Initiative...
November 2017: Journal of Psychiatric Practice
https://www.readbyqxmd.com/read/29300899/tissue-distribution-of-suvorexant-in-three-forensic-autopsy-cases
#9
Brian Waters, Kenji Hara, Natsuki Ikematsu, Mio Takayama, Aya Matsusue, Masayuki Kashiwagi, Shin-Ichi Kubo
Suvorexant (Belsomra®) is a relatively new insomnia medication that has been available in USA and Japan since 2014. It is a dual orexin receptor antagonist that promotes sleep by inhibiting the binding of orexin neurons to the OX1R and OX2R receptors. In this report, we describe the detection and quantitation of suvorexant from the postmortem specimens of three separate autopsy cases handled by our department. Suvorexant was identified by fast gas chromatography/mass spectrometry during routine screening, and quantitated by a fully validated liquid chromatography-tandem mass spectroscopy method...
December 28, 2017: Journal of Analytical Toxicology
https://www.readbyqxmd.com/read/29289556/chronopathophysiological-implications-of-orexin-in-sleep-disturbances-and-lifestyle-related-disorders
#10
REVIEW
Hiroshi Tsuneki, Tsutomu Wada, Toshiyasu Sasaoka
Sleep, a mysterious behavior, has recently been recognized as a crucial factor for health and longevity. The daily sleep/wake cycle provides the basis of biorhythms controlling whole-body homeostasis and homeodynamics; therefore, disruption of sleep causes several physical and psychological disorders, including cardiovascular disease, obesity, diabetes, cancer, anxiety, depression, and cognitive dysfunction. However, the mechanism linking sleep disturbances and sleep-related disorders remains unknown. Orexin (also known as hypocretin) is a neuropeptide produced in the hypothalamus...
December 28, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29259622/noni-morinda-citrifolia-modulates-the-hypothalamic-expression-of-stress-and-metabolic-related-genes-in-broilers-exposed-to-acute-heat-stress
#11
Hossein Rajaei-Sharifabadi, Laura Ellestad, Tom Porter, Annie Donoghue, Walter G Bottje, Sami Dridi
Heat stress (HS) adversely affects growth performance and inflicts heavy economic losses to the poultry industry. There is, therefore, a critical need to identify new alternative strategies to alleviate the negative effects induced by HS. The tropic medicinal plant, Morinda citrifolia (Noni), is being used in livestock nutrition, however the literature is limited and conflicting for its impact on growth performance. The present study aimed to determine the effect of Noni on feeding and drinking behavior as well as on the hypothalamic expression of stress- and metabolic-related genes in broiler chickens exposed to acute HS...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/29258865/role-of-the-orexin-receptors-within-the-nucleus-accumbens-in-the-drug-priming-induced-reinstatement-of-morphine-seeking-in-the-food-deprived-rats
#12
Marjan Sahafzadeh, Saeideh Karimi-Haghighi, Zahra Mousavi, Abbas Haghparast
Orexin plays a key role in mediating stress-induced drug relapse. However, the role of different types of orexinergic receptors that modulate stress-induced drug seeking remains unknown. The nucleus accumbens (NAc) has an important role in the reward system and receives orexinergic projections of the lateral hypothalamus. In addition, orexin interacts with other receptors that are involved in drug reinstatement. Therefore, in the present study, the role of orexin receptors in the NAc in morphine priming- induced reinstatement and the effect of food deprivation (FD) on drug reinstatement were examined...
December 16, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/29250792/increased-acetylcholine-and-glutamate-efflux-in-the-prefrontal-cortex-following-intranasal-orexin-a-hypocretin-1
#13
Coleman B Calva, Habiba Fayyaz, Jim R Fadel
Orexin/hypocretin neurons of the lateral hypothalamus and perifornical area (LH/PFA) are integrators of physiological function. Previous work from our lab and others has shown the importance of orexin transmission in cognition. Age-related reductions in markers of orexin function further suggest that this neuropeptide may be a useful target for the treatment of age-related cognitive dysfunction. Intranasal administration of orexin-A (OxA) has shown promise as a therapeutic option for cognitive dysfunction. However, the neurochemical mechanisms of intranasal OxA administration are not fully understood...
December 18, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29246398/doca-salt-hypertension-alters-period1-and-orexin-related-gene-expression-in-the-medulla-and-hypothalamus-of-male-rats-diurnal-influences
#14
M E Hernandez, J M Watkins, J Vu, L F Hayward
In peripheral tissues, aldosterone alters expression of multiple genes, including the clock gene Period 1 (Per1), 11 beta-hydroxysteroid dehydrogenase-2 (11-HSD2), and α-ENAC, the epithelial sodium channel subunit. We evaluated the impact of chronic aldosterone exposure (DOCA) and salt intake on nocturnal changes in gene expression in the male Sprague Dawley rat brain. Additionally, genes associated with the orexin (ORX) system were also evaluated based on the role of this neuropeptide in arousal, feeding and hypertension and an interconnection with Per1 expression...
December 9, 2017: Autonomic Neuroscience: Basic & Clinical
https://www.readbyqxmd.com/read/29237551/dose-dependent-and-opposite-effects-of-orexin-a-on-prepulse-inhibition-response-in-sleep-deprived-and-non-sleep-deprived-rats
#15
Pınar Öz, H Kübra Gökalp, Tansu Göver, Tayfun Uzbay
Orexin is a novel neurotransmitter released from lateral hypothalamus, that is a crucial modulator in sleep/wakefulness system. Recent studies also suggest its possible role in the neurodevelopmental disorders, such as schizophrenia. Our study consists of two experiments, where we investigate the effect of orexin A (OXA), one of two isoforms of orexin that can pass blood brain barrier, on the prepulse inhibition of acoustic startle reflex. The first experiment tested the effect of OXA on PPI response of non-sleep-deprived rats via intraperitoneal injection 30min before testing...
December 10, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/29230167/changes-in-the-cholinergic-catecholaminergic-orexinergic-and-serotonergic-structures-forming-part-of-the-sleep-systems-of-adult-mice-exposed-to-intrauterine-alcohol
#16
Oladiran I Olateju, Adhil Bhagwandin, Amadi O Ihunwo, Paul R Manger
We examined the effect of chronic prenatal alcohol exposure on certain neuronal systems involved with the sleep-wake cycle of C57BL/6J mice exposed to prenatal alcohol once they had reached 56 days post-natal. Pregnant mice were exposed to alcohol, through oral gavage, on gestational days 7-16, with recorded blood alcohol concentration (BAC)s averaging 1.84 mg/ml (chronic alcohol group, CA). Two control groups, an oral gavage sucrose control group (chronic alcohol control group, CAc) and a non-treated control group (NTc), were also examined...
2017: Frontiers in Neuroanatomy
https://www.readbyqxmd.com/read/29225076/crystal-structures-of-human-orexin-2-receptor-bound-to-the-subtype-selective-antagonist-empa
#17
Ryoji Suno, Kanako Terakado Kimura, Takanori Nakane, Keitaro Yamashita, Junmei Wang, Takaaki Fujiwara, Yasuaki Yamanaka, Dohyun Im, Shoichiro Horita, Hirokazu Tsujimoto, Maki S Tawaramoto, Takatsugu Hirokawa, Eriko Nango, Kensuke Tono, Takashi Kameshima, Takaki Hatsui, Yasumasa Joti, Makina Yabashi, Keiko Shimamoto, Masaki Yamamoto, Daniel M Rosenbaum, So Iwata, Tatsuro Shimamura, Takuya Kobayashi
Orexin peptides in the brain regulate physiological functions such as the sleep-wake cycle, and are thus drug targets for the treatment of insomnia. Using serial femtosecond crystallography and multi-crystal data collection with a synchrotron light source, we determined structures of human orexin 2 receptor in complex with the subtype-selective antagonist EMPA (N-ethyl-2-[(6-methoxy-pyridin-3-yl)-(toluene-2-sulfonyl)-amino]-N-pyridin-3-ylmethyl-acetamide) at 2.30-Å and 1.96-Å resolution. In comparison with the non-subtype-selective antagonist suvorexant, EMPA contacted fewer residues through hydrogen bonds at the orthosteric site, explaining the faster dissociation rate...
November 27, 2017: Structure
https://www.readbyqxmd.com/read/29210184/sympathetic-nerve-activity-and-neuro-inflammation-who-is-in-the-driver-s-seat
#18
EDITORIAL
Snigdha Mukerjee, Eric Lazartigues
The current study by Fan et al.[1] in this issue of Acta Physiologica entitled 'Orexin A increases sympathetic nerve activity through promoting expression of proinflammatory cytokines in Sprague-Dawley rats' sheds some light on the potential signaling pathways leading to cardiovascular activation with regards to increased sympathetic activity and neuro-inflammation and provide an interesting model for future work testing the neuro-inflammation-driven hypertension hypothesis. This article is protected by copyright...
December 5, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/29207107/modular-organization-of-a-hypocretin-gene-minimal-promoter
#19
Adriana Sánchez-García, Griselda A Cabral-Pacheco, Viviana C Zomosa-Signoret, Rocío Ortiz-López, Alberto Camacho, Paulo M Tabera-Tarello, José A Garnica-López, Román Vidaltamayo
Orexins or hypocretins are neurotransmitters produced by a small population of neurons in the lateral hypothalamus. This family of peptides modulates sleep‑wake cycle, arousal and feeding behaviors; however, the mechanisms regulating their expression remain to be fully elucidated. There is an interest in defining the key molecular elements in orexin regulation, as these may serve to identify targets for generating novel therapies for sleep disorders, obesity and addiction. Our previous studies showed that the expression of orexin was decreased in mice carrying null‑mutations of the transcription factor early B‑cell factor 2 (ebf2) and that the promoter region of the prepro‑orexin (Hcrt) gene contained two putative ebf‑binding sites, termed olf‑1 sites...
November 22, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29203229/effects-on-hedonic-feeding-energy-expenditure-and-balance-of-the-non-opioid-peptide-dyn-a2-17
#20
B Alvarez, T Barrientos, L Gac, J A Teske, C E Perez-Leighton
The dynorphin (DYN) peptide family includes opioid and non-opioid peptides, yet the physiological role of the non-opioid DYN peptides remains poorly understood. Recent evidence shows that administering the non-opioid peptide DYN-A2-17 into the paraventricular hypothalamic nucleus (PVN) simultaneously increased short-term intake of standard rodent chow and spontaneous physical activity (SPA). The present studies aimed to expand upon the mechanisms and role of DYN-A2-17 on food intake and energy expenditure. Injection of DYN-A2-17 in PVN increased SPA, energy expenditure and wheel running in the absence of food...
December 1, 2017: Neuroscience
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