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M Sassek, E Pruszynska-Oszmalek, K W Nowak
The physiology of porcine pancreatic islets is poorly understood. Orexin A is one of important agents regulating the physiology of porcine pancreatic islets. This study aimed to determine the potential effect of orexin A on the functioning of porcine pancreatic islets. Orexin receptor localization was done by PCR (polymerase chain reaction) and Western Blot, both in pancreatic isolated islets and whole pancreas. Secretion of insulin and glucagon from islets after orexin-A treatment was assayed. The viability of pig pancreatic islet cells and level of cleaved/total caspase 3 protein were measured by MTT test (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and Western blotting, respectively...
December 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
Shiho Fujita, Toru Hasegawa, Yuki Nishiyama, Satoshi Fujisawa, Yasuhiro Nakano, Takahiro Nada, Nahoko Iwata, Yasuhiko Kamada, Hisashi Masuyama, Fumio Otsuka
The involvement of orexins in reproductive function has been gradually uncovered. However, the functional role of orexins in ovarian steroidogenesis remains unclear. In the present study, we investigated the effects of orexin A on ovarian steroidogenesis by using rat primary granulosa cells that express both OX1 and OX2 receptors for orexins. Treatment with orexin A enhanced progesterone, but not estradiol, biosynthesis induced by FSH, whereas it did not affect basal levels of progesterone or estradiol. In accordance with the effects on steroidogenesis, orexin A increased the mRNA levels of progesterogenic enzymes, including StAR, P450scc and 3βHSD, but not P450arom, and cellular cAMP synthesis induced by FSH...
March 12, 2018: Journal of Steroid Biochemistry and Molecular Biology
Oscar Arias-Carrion, Emmanuel Ortega-Robles, Benito de Celis-Alonso, Artur Palasz, Eric Murillo-Rodriguez, Miguel A Mendez-Rojas, Jose Salas-Pacheco, Elias Manjarrez
Adult neurogenesis, a specific form of brain plasticity in mammals occurring in the subventricular zone, is subject to complex regulations. Hypocretin/orexin neurons are implicated in the regulation of sleep and arousal states among other functions. Here, we found orexin afferent projections in the rat subventricular zone, which is a neurogenic region. We therefore studied in detail the origin of the orexinergic innervation to the subventricular zone in rats. Post-mortem retrograde tracing combined with immunofluorescence procedures indicate orexinergic projections toward the subventricular zone...
March 13, 2018: CNS & Neurological Disorders Drug Targets
Antonietta Messina, Ilaria Bitetti, Francesco Precenzano, Diego Iacono, Giovanni Messina, Michele Roccella, Lucia Parisi, Margherita Salerno, Anna Valenzano, Agata Maltese, Monica Salerno, Francesco Sessa, Giuseppe Davide Albano, Rosa Marotta, Ines Villano, Gabriella Marsala, Christian Zammit, Francesco Lavano, Marcellino Monda, Giuseppe Cibelli, Serena Marianna Lavano, Beatrice Gallai, Roberto Toraldo, Vincenzo Monda, Marco Carotenuto
Introduction: Sleep and migraine share a common pathophysiological substrate, although the underlying mechanisms are unknown. The serotonergic and orexinergic systems are both involved in the regulation of sleep/wake cycle, and numerous studies show that both are involved in the migraine etiopathogenesis. These two systems are anatomically and functionally interconnected. Our hypothesis is that in migraine a dysfunction of orexinergic projections on the median raphe (MR) nuclei, interfering with serotonergic regulation, may cause Non-Rapid Eye Movement parasomnias, such as somnambulism...
2018: Frontiers in Neurology
Claudia Laperchia, Yuan-Zhong Xu, Dieudonné Mumba Ngoyi, Tiziana Cotrufo, Marina Bentivoglio
Neuron populations of the lateral hypothalamus which synthesize the orexin (OX)/hypocretin or melanin-concentrating hormone (MCH) peptides play crucial, reciprocal roles in regulating wake stability and sleep. The disease human African trypanosomiasis (HAT), also called sleeping sickness, caused by extracellular Trypanosoma brucei ( T. b .) parasites, leads to characteristic sleep-wake cycle disruption and narcoleptic-like alterations of the sleep structure. Previous studies have revealed damage of OX and MCH neurons during systemic infection of laboratory rodents with the non-human pathogenic T...
2018: Frontiers in Neuroanatomy
Arisa Hirano, Pei-Ken Hsu, Luoying Zhang, Lijuan Xing, Thomas McMahon, Maya Yamazaki, Louis J Ptáček, Ying-Hui Fu
Adequate sleep is essential for physical and mental health. We previously identified a missense mutation in the human DEC2 gene ( BHLHE41 ) leading to the familial natural short sleep behavioral trait. DEC2 is a transcription factor regulating the circadian clock in mammals, although its role in sleep regulation has been unclear. Here we report that prepro-orexin , also known as hypocretin ( Hcrt ), gene expression is increased in the mouse model expressing the mutant h DEC2 transgene (h DEC2-P384R ). Prepro-orexin encodes a precursor protein of a neuropeptide producing orexin A and B (hcrt1 and hcrt2), which is enriched in the hypothalamus and regulates maintenance of arousal...
March 12, 2018: Proceedings of the National Academy of Sciences of the United States of America
Rachel I Anderson, David E Moorman, Howard C Becker
Understanding the neural systems that drive alcohol motivation and are disrupted in alcohol use disorders is of critical importance in developing novel treatments. The dynorphin and orexin/hypocretin neuropeptide systems are particularly relevant with respect to alcohol use and misuse. Both systems are strongly associated with alcohol-seeking behaviors, particularly in cases of high levels of alcohol use as seen in dependence. Furthermore, both systems also play a role in stress and anxiety, indicating that disruption of these systems may underlie long-term homeostatic dysregulation seen in alcohol use disorders...
March 11, 2018: Handbook of Experimental Pharmacology
Alexis Roman, Soraya Meftah, Sébastien Arthaud, Pierre-Hervé Luppi, Christelle Peyron
Narcolepsy type 1 is a disabling disorder with four primary symptoms: excessive-daytime-sleepiness, cataplexy, hypnagogic hallucinations and sleep paralysis. The three latter symptoms together with a short REM sleep latency have suggested impairment in REM sleep homeostatic regulation with an enhanced propensity for (i.e. tendency to enter) REM sleep. To test this hypothesis, we challenged REM sleep homeostatic regulation in a recognized model of narcolepsy, the orexin knock-out (Orex-KO) mice and their wild-type (WT) littermates...
March 7, 2018: Sleep
Satoshi Toyama, Naohito Shimoyama, Yugo Tagaito, Hiroshi Nagase, Tsuyoshi Saitoh, Masashi Yanagisawa, Megumi Shimoyama
BACKGROUND: Sleepiness and decrease in attention are dose-limiting side effects of opioids. The orexin/hypocretin system plays an important role in maintaining wakefulness. This study aimed to explore the potential of a nonpeptide orexin receptor agonist to alleviate morphine-induced sedative effects. METHODS: Morphine sedative effects were evaluated as changes in electroencephalogram (EEG), locomotor activity, and acoustic startle response in rats (n = 5 to 9 per group)...
March 8, 2018: Anesthesiology
Diana Y Wei, Rigmor H Jensen
Trigeminal autonomic cephalalgia (TAC) encompasses 4 unique primary headache types: cluster headache, paroxysmal hemicrania, hemicrania continua, and short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing and short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms. They are grouped on the basis of their shared clinical features of unilateral headache of varying durations and ipsilateral cranial autonomic symptoms. The shared clinical features reflect the underlying activation of the trigeminal-autonomic reflex...
March 7, 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
Sheldon H Preskorn
This column is the fifth in a series examining the advances being made in central nervous system drug development because of advances in molecular pharmacology and an improved understanding of the neurobiology underlying disturbances in brain function including psychiatric illnesses. This column covers the special animal and human studies conducted as part of the development of suvorexant, which is the first in the class of dual orexin 1 and 2 receptor antagonists to be approved; it has an indication for the treatment of disturbances in sleep onset and maintenance...
March 2018: Journal of Psychiatric Practice
David E Moorman
The hypocretin/orexin (ORX) system has been repeatedly demonstrated to regulate motivation for drugs of abuse, including alcohol. In particular, ORX seems to be critically involved in highly motivated behaviors, as is observed in high-seeking individuals in a population, in the seeking of highly palatable substances, and in models of dependence. It seems logical that this system could be considered as a potential target for treatment for addiction, particularly alcohol addiction, as ORX pharmacological manipulations significantly reduce drinking...
March 6, 2018: Psychopharmacology
Giovanna Liguori, Simona Tafuri, Chika Miyoshi, Masashi Yanagisawa, Caterina Squillacioti, Valeria De Pasquale, Nicola Mirabella, Alfredo Vittoria, Anna Costagliola
The peptides orexin A (OXA) and orexin B (OXB) derived from the proteolytic cleavage of a common precursor molecule, prepro-orexin, were originally described in the rat hypothalamus. Successively, they have been found in many other brain regions as well as in peripheral organs of mammals and other less evolved animals. The widespread localization of orexins accounts for the multiple activities that they exert in the body, including the regulation of energy homeostasis, feeding, metabolism, sleep and arousal, stress, addiction, and cardiovascular and endocrine functions...
February 26, 2018: Acta Histochemica
Tobias Atkin, Stefano Comai, Gabriella Gobbi
Although the GABAergic benzodiazepines (BZDs) and Z-drugs (zolpidem, zopiclone, and zaleplon) are FDA-approved for insomnia disorders with a strong evidence base, they have many side effects, including cognitive impairment, tolerance, rebound insomnia upon discontinuation, car accidents/falls, abuse, and dependence liability. Consequently, the clinical use of off-label drugs and novel drugs that do not target the GABAergic system is increasing. The purpose of this review is to analyze the neurobiological and clinical evidence of pharmacological treatments of insomnia, excluding the BZDs and Z-drugs...
April 2018: Pharmacological Reviews
Koichiro Ogawa, Hidetaka Suga, Chikafumi Ozone, Mayu Sakakibara, Tomiko Yamada, Mayuko Kano, Kazuki Mitsumoto, Takatoshi Kasai, Yu Kodani, Hiroshi Nagasaki, Naoki Yamamoto, Daisuke Hagiwara, Motomitsu Goto, Ryoichi Banno, Yoshihisa Sugimura, Hiroshi Arima
Arginine-vasopressin (AVP) neurons exist in the hypothalamus, a major region of the diencephalon, and play an essential role in water balance. Here, we established the differentiation method for AVP-secreting neurons from human embryonic stem cells (hESCs) by recapitulating in vitro the in vivo embryonic developmental processes of AVP neurons. At first, the differentiation efficiency was improved. That was achieved through the optimization of the culture condition for obtaining dorsal hypothalamic progenitors...
February 26, 2018: Scientific Reports
T W Robbins
This article critically reviews evidence relating temperamental traits and personality factors to the monoamine neurotransmitters, especially dopamine and serotonin. The genetic evidence is not yet considered to be conclusive and it is argued that basic neuroscience research on the neural basis of behaviour in experimental animals should be taken more into account. While questionnaire and lexical methodology including the 'Five Factor' theory has been informative (mostly for the traits relevant to social functioning, i...
April 19, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
Giovanna Liguori, Caterina Squillacioti, Loredana Assisi, Alessandra Pelagalli, Alfredo Vittoria, Anna Costagliola, Nicola Mirabella
BACKGROUND: Cryptorchidism is one of the most common birth disorders of the male reproductive system identified in dogs and other mammals. This condition is characterised by the absence of one (unilateral) or both (bilateral) gonads from the scrotum. The peptides orexin A (OxA) and B (OxB) were obtained by post-transcriptional proteolytic cleavage of a precursor molecule, called prepro-orexin. These substances bind two types of G-coupled receptors called receptor 1 (OX1R) and 2 (OX2R) for orexins...
February 27, 2018: BMC Veterinary Research
D Joshi, S K Singh
Orexin A, a hypothalamic neuropeptide, regulates food intake and sleep-wake cycle by binding to orexin receptor 1. Besides brain, orexin A and orexin receptor 1 are also present in peripheral organs. In our earlier studies, localization and expression of orexin A and orexin receptor 1 have been shown in adult mouse testis, and further their role in testicular development in neonatal mouse was also demonstrated. In this study, role of orexin A and orexin receptor 1 in the testis of adult mouse by blocking binding of orexin A to orexin receptor 1 using an orexin receptor 1 antagonist, SB-334867, was investigated under in vivo and ex vivo conditions...
February 26, 2018: Andrology
Limei Zhang, Vito S Hernández, Jerome D Swinny, Anil K Verma, Torsten Giesecke, Andrew C Emery, Kerim Mutig, Luis M Garcia-Segura, Lee E Eiden
The lateral habenula (LHb) has a key role in integrating a variety of neural circuits associated with reward and aversive behaviors. There is limited information about how the different cell types and neuronal circuits within the LHb coordinate physiological and motivational states. Here, we report a cell type in the medial division of the LHb (LHbM) in male rats that is distinguished by: (1) a molecular signature for GABAergic neurotransmission (Slc32a1/VGAT) and estrogen receptor (Esr1/ERα) expression, at both mRNA and protein levels, as well as the mRNA for vesicular glutamate transporter Slc17a6/VGLUT2, which we term the GABAergic estrogen-receptive neuron (GERN); (2) its axonal projection patterns, identified by in vivo juxtacellular labeling, to both local LHb and to midbrain modulatory systems; and (3) its somatic expression of receptors for vasopressin, serotonin and dopamine, and mRNA for orexin receptor 2...
February 26, 2018: Translational Psychiatry
Toshikatsu Okumura, Tsukasa Nozu, Shima Kumei, Kaoru Takakusaki, Masumi Ohhira
Increasing evidence implicates brain ghrelin in a wide variety of physiological functions. Among its gastrointestinal functions, ghrelin is known to act centrally to regulate gastrointestinal motility. Visceral sensation is one of the key gastrointestinal functions controlled by the central nervous system. Little is, however, known about the role of central ghrelin in visceral sensation. The present study thus aimed to clarify whether brain ghrelin is involved in visceral sensation. Visceral sensation was evaluated by the colonic distension-induced abdominal withdrawal reflex (AWR) in conscious rats...
February 21, 2018: Brain Research
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