Impaired orexin receptor expression in the Kölliker-Fuse nucleus in sudden infant death syndrome: possible involvement of this nucleus in arousal pathophysiology

• Published in: Neurological research (New York) Vol. 38; no. 8; p. 706
• Main Authors: Lavezzi, Anna Maria, Ferrero, Stefano, Roncati, Luca, Matturri, Luigi, Pusiol, Teresa
• Format: Journal Article
• Language: English
• Published: England 02.08.2016
• Subjects: Female; Glial Fibrillary Acidic Protein - metabolism; Humans; Infant; Kolliker-Fuse Nucleus - metabolism; Kolliker-Fuse Nucleus - pathology; Kolliker-Fuse Nucleus - physiopathology; Male; Neurons - metabolism; Orexin Receptors - metabolism; Phosphopyruvate Hydratase - metabolism; Sudden Infant Death - pathology; GFAP= glial fibrillary acid protein; BDNF= brain-derived neurotrophic factor; LC= locus coeruleus; SIDS; Neuropathology; Brainstem; CPAP= continuous positive airway pressure; F/PFc= Facial/Parafacial complex; KFN= Kölliker–Fuse nucleus; NeuN= neuronal nuclear antigen; ILN= intermediolateral nucleus; Kölliker–Fuse nucleus; Ox= Orexin; TSN= tractus solitarius nucleus; Arousal; RN= respiratory network; GC/MS= gas chromatography/mass spectrometry; OxR= Orexin receptor; SIDS= sudden infant death syndrome; pBN= pre-Bötzinger nucleus; Orexin; ABC= avidin-biotin complex
• ISSN: 1743-1328
• DOI: 10.1080/01616412.2016.1201632

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. 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. An intense orexin-1 innervation around the KF neurons has been detected in almost all the controls and only in 20% of SIDS cases. 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.