Altered 5-HT2A/C receptor binding in the medulla oblongata in the sudden infant death syndrome (SIDS): Part I. Tissue-based evidence for serotonin receptor signaling abnormalities in cardiorespiratory- and arousal-related circuits

• Published in: Journal of neuropathology and experimental neurology Vol. 82; no. 6; pp. 467 - 482
• Main Authors: Haynes, Robin L, Trachtenberg, Felicia, Darnall, Ryan, Haas, Elisabeth A, Goldstein, Richard D, Mena, Othon J, Krous, Henry F, Kinney, Hannah C
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 25-05-2023
• Subjects: Arousal; Brain; Brain Stem; Humans; Medulla Oblongata; SIDS; Sudden Infant Death; Sudden infant death syndrome; Autoresuscitation; Gasping; Ventral medulla; Cardiac and respiratory coupling; Olivocerebellar pathways; Hypotension
• ISSN: 0022-3069; 1554-6578; 1554-6578
• DOI: 10.1093/jnen/nlad030

Abstract
The sudden infant death syndrome (SIDS), the leading cause of postneonatal infant mortality in the United States, is typically associated with a sleep period. Previously, we showed evidence of serotonergic abnormalities in the medulla (e.g. altered serotonin (5-HT)1A receptor binding), in SIDS cases. In rodents, 5-HT2A/C receptor signaling contributes to arousal and autoresuscitation, protecting brain oxygen status during sleep. Nonetheless, the role of 5-HT2A/C receptors in the pathophysiology of SIDS is unclear. We hypothesize that in SIDS, 5-HT2A/C receptor binding is altered in medullary nuclei that are key for arousal and autoresuscitation. Here, we report altered 5-HT2A/C binding in several key medullary nuclei in SIDS cases (n = 58) compared to controls (n = 12). In some nuclei the reduced 5-HT2A/C and 5-HT1A binding overlapped, suggesting abnormal 5-HT receptor interactions. The data presented here (Part 1) suggest that a subset of SIDS is due in part to abnormal 5-HT2A/C and 5-HT1A signaling across multiple medullary nuclei vital for arousal and autoresuscitation. In Part II to follow, we highlight 8 medullary subnetworks with altered 5-HT receptor binding in SIDS. We propose the existence of an integrative brainstem network that fails to facilitate arousal and/or autoresuscitation in SIDS cases.