title: Orexin Plays a Role in Growth Impediment Induced by Obstructive Sleep Breathing in Rats.
abstract: OBJECTIVE
  The mechanisms linking sleep disordered breathing with impairment of sleep and bone metabolism/architecture are poorly understood. Here, we explored the role of the neuropeptide orexin, a respiratory homeostasis modulator, in growth retardation induced in an upper airway obstructed (AO) rat model.
  
  
  METHODS
  The tracheae of 22-day-old rats were narrowed; AO and sham-control animals were monitored for 5 to 7 w. Growth parameters, food intake, sleep/wake activity, and serum hormones were measured. After euthanasia, growth plate (GP) histology, morphometry, orexin receptors (OXR), and related mediators were analyzed. The effect of dual orexin receptor antagonist (almorexant 300 mg/kg) on sleep and GP histology were also investigated.
  
  
  RESULTS
  The AO group slept 32% less; the time spent in slow wave and paradoxical sleep during light period and slow wave activity was reduced. The AO group gained 46% less body weight compared to the control group, despite elevated food intake; plasma ghrelin increased by 275% and leptin level decreased by 44%. The impediment of bone elongation and bone mass was followed by a 200% increase in OX1R and 38% reduction of local GP ghrelin proteins and growth hormone secretagogue receptor 1a. Sry-related transcription factor nine (Sox9), a molecule mediating cartilage ossification, was downregulated and the level of transcription factor peroxisome proliferator-activated receptor gamma was upregulated, explaining the bone architecture abnormalities. Administration of almorexant restored sleep and improved GP width in AO animals.
  
  
  CONCLUSIONS
  In AO animals, enhanced expression of orexin and OX1R plays a role in respiratory induced sleep and growth abnormalities.
authors.affiliation: Shraga Segal Department of Microbiology and Immunology, Ben-Gurion University of the Negev, Beer-Sheva, Israel.|Sleep-Wake Disorders Unit, Soroka University Medical Center, Beer-Sheva, Israel.|Department of Physiology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Ariel
authors.initials: A
authors.lastname: Tarasiuk
authors.affiliation: Shraga Segal Department of Microbiology and Immunology, Ben-Gurion University of the Negev, Beer-Sheva, Israel.|Department of Physiology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Avishag
authors.initials: A
authors.lastname: Levi
authors.affiliation: Shraga Segal Department of Microbiology and Immunology, Ben-Gurion University of the Negev, Beer-Sheva, Israel.|Department of Physiology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Mohammad H
authors.initials: MH
authors.lastname: Assadi
authors.affiliation: Shraga Segal Department of Microbiology and Immunology, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Ariel
authors.initials: A
authors.lastname: Troib
authors.affiliation: Shraga Segal Department of Microbiology and Immunology, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Yael
authors.initials: Y
authors.lastname: Segev
mesh_terms: D000081:Acetamides / Q000494:pharmacology; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001846:Bone Development / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D054439:Ghrelin / Q000097:blood; D006130:Growth Disorders / Q000097:blood / Q000209:etiology* / Q000378:metabolism*; D006706:Homeostasis / Q000187:drug effects; D007546:Isoquinolines / Q000494:pharmacology; D020738:Leptin / Q000097:blood; D008297:Male; D000068796:Orexin Receptor Antagonists / Q000494:pharmacology; D064446:Orexin Receptors / Q000378:metabolism*; D000068797:Orexins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012119:Respiration; D012890:Sleep / Q000187:drug effects; D012891:Sleep Apnea Syndromes / Q000097:blood / Q000150:complications*; D012895:Sleep, REM / Q000187:drug effects; D014851:Wakefulness / Q000187:drug effects
chemical_list: D000081:Acetamides; D054439:Ghrelin; D007546:Isoquinolines; D020738:Leptin; D000068796:Orexin Receptor Antagonists; D064446:Orexin Receptors; D000068797:Orexins; C519150:almorexant
keywords: growth; orexin; rat; sleep; upper airway loading