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Sporadic Autonomic Dysregulation and Death Associated with Excessive Serotonin Autoinhibition

Enrica Audero,1 Elisabetta Coppi,2 Boris Mlinar,2 Tiziana Rossetti,1 Antonio Caprioli,3 Mumna Al Banchaabouchi,1 Renato Corradetti,2 Cornelius Gross1*

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.

1 Mouse Biology Unit, European Molecular Biology Laboratory (EMBL), Via Ramarini 32, 00015 Monterotondo, Italy.
2 Department of Preclinical and Clinical Pharmacology, University of Firenze, Viale Giacoro Pieraccini 6, 50139 Firenze, Italy.
3 Laboratory of Behavioural Neuropharmacology, Sigma-Tau SpA, Via Pontina Kilometer 30.400, 00040 Pomezia, Italy.

* To whom correspondence should be addressed.
E-mail: gross@embl.it

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