title: Impaired orexin receptor expression in the Kölliker-Fuse nucleus in sudden infant death syndrome: possible involvement of this nucleus in arousal pathophysiology.
abstract: OBJECTIVE
  As well known, the sudden infant death syndrome (SIDS) is characterized by the sudden death of a seemingly healthy infant during sleep, frequently resulted from a deficit in arousal phase. Awakening from sleep requires a fully developed and functioning neuronal respiratory network to modulate the ventilation as needed. The pontine Kölliker-Fuse nucleus (KFN) plays a pivotal role in breathing control, thanks to its interconnections with the widespread serotonin and noradrenaline neurons in the brainstem. Numerous studies to date have focused on the implication of orexin, a neuropeptide synthesized by neurons of the lateral hypothalamus, with major projections to the brainstem raphé nuclei and locus coeruleus, in arousal, a neurobiological process closely linked to breathing modifications. The aim of our research has been to demonstrate that also the KFN is a fundamental component of the orexin system, actively involved in arousal.
  
  
  METHODS
  We have evaluated the expression and distribution of the orexin receptors (orexin-1 and orexin-2 receptors) particularly in the rostral pons, where the KFN is located, of 25 SIDS cases and 18 controls.
  
  
  RESULTS
  An intense orexin-1 innervation around the KF neurons has been detected in almost all the controls and only in 20% of SIDS cases.
  
  
  CONCLUSIONS
  On the basis of these results, we believe that: (1) the KFN plays a leading role not only in providing a regular breathing rhythm but also in the coordination of the sleep-to-wake transition; (2) a defective orexin expression in the KFN could prevent arousal, thus assuming a crucial importance in causing SIDS.
authors.affiliation: a 'Lino Rossi' Research Center for the study and prevention of unexpected perinatal death and SIDS, Department of Biomedical, Surgical and Dental Sciences , University of Milan , Milan , Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Lavezzi
authors.affiliation: a 'Lino Rossi' Research Center for the study and prevention of unexpected perinatal death and SIDS, Department of Biomedical, Surgical and Dental Sciences , University of Milan , Milan , Italy.|b Division of Pathology , Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico , Milan , Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Ferrero
authors.affiliation: c Institute of Pathology, Hospital of Rovereto (Trento) , Italy.|d Department of Diagnostic and Clinical Medicine and of Public Health, Section of Pathology , University of Modena and Reggio Emilia, Policlinico Hospital , Modena , Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Roncati
authors.affiliation: a 'Lino Rossi' Research Center for the study and prevention of unexpected perinatal death and SIDS, Department of Biomedical, Surgical and Dental Sciences , University of Milan , Milan , Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Matturri
authors.affiliation: c Institute of Pathology, Hospital of Rovereto (Trento) , Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Pusiol
mesh_terms: D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007223:Infant; D065836:Kolliker-Fuse Nucleus / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D009474:Neurons / Q000378:metabolism; D064446:Orexin Receptors / Q000378:metabolism*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D013398:Sudden Infant Death / Q000473:pathology*
chemical_list: D005904:Glial Fibrillary Acidic Protein; D064446:Orexin Receptors; D010751:Phosphopyruvate Hydratase
keywords: ABC= avidin-biotin complex; Arousal; BDNF= brain-derived neurotrophic factor; Brainstem; CPAP= continuous positive airway pressure; F/PFc= Facial/Parafacial complex; GC/MS= gas chromatography/mass spectrometry; GFAP= glial fibrillary acid protein; ILN= intermediolateral nucleus; KFN= Kölliker–Fuse nucleus; Kölliker–Fuse nucleus; LC= locus coeruleus; NeuN= neuronal nuclear antigen; Neuropathology; Orexin; Ox= Orexin; OxR= Orexin receptor; RN= respiratory network; SIDS; SIDS= sudden infant death syndrome; TSN= tractus solitarius nucleus.; pBN= pre-Bötzinger nucleus