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BioMol Concepts, Vol. 3 (2012), pp. 447–463 • Copyright © by Walter de Gruyter • Berlin • Boston. DOI 10.1515/bmc-2012-0013 Review Recent progress in orexin/hypocretin physiology and pharmacology Jyrki P. Kukkonen Biochemistry and Cell Biology , Department of Veterinary Biosciences, FIN-00014 University of Helsinki , Finland e-mail: Abstract Orexin peptides and their cognate receptors were discovered 14 years ago. They soon took a very central position in the regulation of sleep and wakefulness. Active studies have

emerged as a promising new model for studying sleep, its changes with age, and the impact of sleep alterations on cognitive function. Recent studies of this diurnal vertebrate have provided new insights into the dual role of the pineal hormone melatonin and its receptors, regulating sleep in diurnal vertebrates through both homeostatic and circadian mechanisms. Research in zebrafi sh has also revealed interactions between melatonin and the hypocretin/orexin system, another important sleep- wake modulator. Future investigations should benefi t from the

dyslipidemia: studies of metabolic traits in 7,683 white Danish subjects. Diabetes. 2008; 57(5): 1427-1432. 9. Mathews ST, Singh GP, Ranalletta M, Cintron VJ, Qiang X, Goustin AS, et al. Improved insulin sensitivity and resistance to weight gain in mice null for the AHSG gene. Diabetes. 2002; 51(8): 2450-2458. 10. Ganjavi H, Shapiro CM. Hypocretin/Orexin: a molecular link between sleep, energy regulation, and pleasure. J Neuropsychiatry Clin Neurosci. 2007; 19(4): 413-419. 11. Sakurai T, Moriguchi T, Furuya K, Kajiwara N, Nakamura T, Yanagisawa M, et al. Structure and

identifiziert, die jeweils verschiedene Funktionen bei der Regulation des Ess- und Schlafverhaltens ( Steculorum et al., 2015 ; Steiger et al., 2011 ; Bonnavion et al., 2016 ) sowie bei defensivem Verhalten ( Lin et al., 2011 ) übernehmen. Im lateralen Hypothalamus co-exprimieren viele Zellen, zusätzlich zu den „schnellen“ Neurotransmittern (Glutamat oder GABA), Neuropeptide wie Orexin/Hypocretin oder MCH (melanin-concentrating hormone) ( Bonnavion et al., 2016 ; Schone und Burdakov, 2012 ). Durch Verabreichung von Neuropeptiden und Studien in Maus-Mutanten wurde bekannt

hypothalamus (LH), in addition to “fast” neurotransmitters (glutamate or GABA), cells co-express neuropeptides, including orexins/hypocretins or MCH (melanin-concentrating hormone) (reviewed in ( Bonnavion et al., 2016 ; Schone and Burdakov, 2012 )). Administration of these neuropeptides as well as studies in mutant mice showed that each of these neuronal groups plays a unique, complementary role in regulation of sleep, feeding and locomotion. For instance, orexins have been implicated in vigilance state control, feeding, exploratory activity and reward processing (reviewed

cant progress has been made in our understanding of the fundamental central nervous system circuitry that reg- ulates body temperature [see refs. (1 – 4) ]. Not surprisingly, the excitatory amino acid glutamate and the inhibitory amino acid GABA are the primary neurotransmitters within the fundamental central neural pathways for thermoregulation. In addition, body temperature can be infl uenced by an exten- sive array of peptides and other central neurotransmitters, including (but not limited to) hypocretin/orexin, galanin, melanin-concentrating hormone

children's future development and must be dealt with rapidly and effectively. Our cohort is obviously too small to draw conclusions. However, we thought it interesting to base upon these four examples a summary of the various currently entertained hypotheses that could link obesity, puberty and narcolepsy, as previously done by Arnulf". Based on the close correlation between human narcolepsy and the human leukocyte antigen (HLA) subtype DQB 1*0602, and the low concordance between identical twins, highly selective, autoimmune- mediated destruction of hypocretin neurons is

, Frauscher B, Kronenberg F, Tafti M, Stiasny-Kolster K, Robyr AC, et al. Daytime sleepiness and the COMT val158met polymorphism in patients with parkinson disease. Sleep 2006 ; 29 : 108 –11. 24. Mignot E, Lammers GJ, Ripley B, Okun M, Nevsimalova S, Overeem S, et al. The role of cerebrospinal fluid hypocretin measurement in the diagnosis of narcolepsy and other hypersomnias. Arch Neurol 2002 ; 59 : 1553 –62. 25. Ripley B, Overeem S, Fujiki N, Nevsimalova S, Uchino M, Yesavage J, et al. CSF hypocretin/orexin levels in narcolepsy and other neurological conditions

Introduction The hypothalamic neuropeptide “orexin A/hypocretin 1” [ 1 ] causes a widespread stimulation of the sympathetic nervous system. This peptide is so named for its control on eating behavior [ 2 ], [ 3 ]. An intracerebroventricular (ICV) administration of orexin A not only affects food intake, but also causes tachycardia [ 4 ], associated with an increase in blood pressure (BP) [ 5 ] and metabolic rate [ 6 ]. These autonomic changes suggest that this peptide is involved in the regulation of autonomic reactions. Orexin A also induces changes in body

PIŚMIENNICTWO 1. Sarnecki J. Zapobieganie SIDS – zalecenia AAP. Stand Med. [Available online]: (accessed on 02.05.2019). 2. Stanisław P. Ocena częstości występowania czynników ryzyka zespołu nagłej śmierci niemowlęcia, Rozprawa doktorska, Poznań 2010. 3. Lancien M, OdiliaInocente C, Dauvilliers Y et al. Low cerebrospinal fluid hypocretin levels during sudden infant death syndrome (SIDS) risk period. Sleep Med. 2017; (33): 57-60. 4. Horne R. Sudden infant death syndrome: current perspectives. Intern Med J. 2019; (49): 433