title: Sporadic autonomic dysregulation and death associated with excessive serotonin autoinhibition.
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.
authors.affiliation: Mouse Biology Unit, European Molecular Biology Laboratory (EMBL), Via Ramarini 32, 00015 Monterotondo, Italy.
authors.forename: Enrica
authors.initials: E
authors.lastname: Audero
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Coppi
authors.forename: Boris
authors.initials: B
authors.lastname: Mlinar
authors.forename: Tiziana
authors.initials: T
authors.lastname: Rossetti
authors.forename: Antonio
authors.initials: A
authors.lastname: Caprioli
authors.forename: Mumna Al
authors.initials: MA
authors.lastname: Banchaabouchi
authors.forename: Renato
authors.initials: R
authors.lastname: Corradetti
authors.forename: Cornelius
authors.initials: C
authors.lastname: Gross
mesh_terms: D000818:Animals; D001341:Autonomic Nervous System / Q000502:physiology*; D017660:Autoreceptors / Q000378:metabolism; D001831:Body Temperature; D004318:Doxycycline / Q000494:pharmacology; D004562:Electrocardiography; D025461:Feedback, Physiological; D006339:Heart Rate; D006706:Homeostasis; D006801:Humans; D007223:Infant; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity; D009433:Neural Inhibition; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology; D011903:Raphe Nuclei / Q000166:cytology / Q000378:metabolism; D044282:Receptor, Serotonin, 5-HT1A / Q000235:genetics / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D013398:Sudden Infant Death / Q000209:etiology*; D013564:Sympathetic Nervous System / Q000502:physiology; D009435:Synaptic Transmission; D014364:Tryptophan / Q000378:metabolism / Q000494:pharmacology
chemical_list: D017660:Autoreceptors; D010879:Piperazines; D011725:Pyridines; D012702:Serotonin Antagonists; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D014364:Tryptophan; D004318:Doxycycline