Sporadic autonomic dysregulation and death associated with excessive serotonin autoinhibition.
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.
Audero
Enrica
E
Mouse Biology Unit, European Molecular Biology Laboratory (EMBL), Via Ramarini 32, 00015 Monterotondo, Italy.
Coppi
Elisabetta
E
Mlinar
Boris
B
Rossetti
Tiziana
T
Caprioli
Antonio
A
Banchaabouchi
Mumna Al
MA
Corradetti
Renato
R
Gross
Cornelius
C
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
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