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Title:
Sporadic Autonomic Dysregulation and Death Associated with Excessive Serotonin Autoinhibition
Authors:
Audero, Enrica; Coppi, Elisabetta; Mlinar, Boris; Rossetti, Tiziana; Caprioli, Antonio; Al Banchaabouchi, Mumna; Corradetti, Renato; Gross, Cornelius
Affiliation:
AA(Mouse Biology Unit, European Molecular Biology Laboratory (EMBL), Via Ramarini 32, 00015 Monterotondo, Italy.), AB(Department of Preclinical and Clinical Pharmacology, University of Firenze, Viale Giacoro Pieraccini 6, 50139 Firenze, Italy.), AC(Department of Preclinical and Clinical Pharmacology, University of Firenze, Viale Giacoro Pieraccini 6, 50139 Firenze, Italy.), AD(Mouse Biology Unit, European Molecular Biology Laboratory (EMBL), Via Ramarini 32, 00015 Monterotondo, Italy.), AE(Laboratory of Behavioural Neuropharmacology, Sigma-Tau SpA, Via Pontina Kilometer 30.400, 00040 Pomezia, Italy.), AF(Mouse Biology Unit, European Molecular Biology Laboratory (EMBL), Via Ramarini 32, 00015 Monterotondo, Italy.), AG(Department of Preclinical and Clinical Pharmacology, University of Firenze, Viale Giacoro Pieraccini 6, 50139 Firenze, Italy.), AH(Mouse Biology Unit, European Molecular Biology Laboratory (EMBL), Via Ramarini 32, 00015 Monterotondo, Italy.)
Publication:
Science, Volume 321, Issue 5885, pp. 130- (2008). (Sci Homepage)
Publication Date:
07/2008
Category:
MEDICINE
Origin:
SCIENCE
Abstract Copyright:
(c) 2008: Science
DOI:
10.1126/science.1157871
Bibliographic Code:
2008Sci...321..130A

Abstract

Sudden infant death syndrome is the leading cause of death in the postneonatal period in developed countries. Postmortem studies show alterations in serotonin neurons in the brainstem of such infants. However, the mechanism by which altered serotonin homeostasis might cause sudden death is unknown. We investigated the consequences of altering the autoinhibitory capacity of serotonin neurons with the reversible overexpression of serotonin 1A autoreceptors in transgenic mice. Overexpressing mice exhibited sporadic bradycardia and hypothermia that occurred during a limited developmental period and frequently progressed to death. Moreover, overexpressing mice failed to activate autonomic target organs in response to environmental challenges. These findings show that excessive serotonin autoinhibition is a risk factor for catastrophic autonomic dysregulation and provide a mechanism for a role of altered serotonin homeostasis in sudden infant death syndrome.
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