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.

Autoresuscitation Cardiac and respiratory coupling Gasping Hypotension Olivocerebellar pathways Ventral medulla

Journal

Journal of neuropathology and experimental neurology
ISSN: 1554-6578
Titre abrégé: J Neuropathol Exp Neurol
Pays: England
ID NLM: 2985192R

Informations de publication

Date de publication:
25 05 2023
Historique:
pmc-release: 25 05 2024
medline: 26 5 2023
pubmed: 25 5 2023
entrez: 25 5 2023
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 37226597
pii: 7177600
doi: 10.1093/jnen/nlad030
pmc: PMC10209647
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

467-482

Subventions

Organisme : NICHD NIH HHS
ID : P01 HD036379
Pays : United States
Organisme : NICHD NIH HHS
ID : P50 HD105351
Pays : United States
Organisme : NICHD NIH HHS
ID : R01HD090064
Pays : United States

Informations de copyright

© The Author(s) 2023. Published by Oxford University Press on behalf of American Association of Neuropathologists, Inc. All rights reserved. For permissions, please email: journals.permissions@oup.com.

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Auteurs

Robin L Haynes (RL)

CJ Murphy Laboratory for SIDS Research, Department of Pathology, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Robert's Program on Sudden Unexpected Death in Pediatrics, Division of General Pediatrics, Department of Pediatrics, Boston Children's Hospital, Boston, Massachusetts, USA.

Felicia Trachtenberg (F)

Carelon Research, Newton, Massachusetts, USA.

Ryan Darnall (R)

CJ Murphy Laboratory for SIDS Research, Department of Pathology, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA.

Elisabeth A Haas (EA)

Department of Research, Rady Children's Hospital, San Diego, California, USA.

Richard D Goldstein (RD)

Robert's Program on Sudden Unexpected Death in Pediatrics, Division of General Pediatrics, Department of Pediatrics, Boston Children's Hospital, Boston, Massachusetts, USA.
Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA.

Othon J Mena (OJ)

San Diego County Medical Examiner Office, San Diego, California, USA.

Henry F Krous (HF)

University of California, San Diego, San Diego, California, USA.
Rady Children's Hospital, San Diego, California, USA.

Hannah C Kinney (HC)

CJ Murphy Laboratory for SIDS Research, Department of Pathology, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Robert's Program on Sudden Unexpected Death in Pediatrics, Division of General Pediatrics, Department of Pediatrics, Boston Children's Hospital, Boston, Massachusetts, USA.

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