Document Detail


Sporadic autonomic dysregulation and death associated with excessive serotonin autoinhibition.
MedLine Citation:
PMID:  18599790     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Enrica Audero; Elisabetta Coppi; Boris Mlinar; Tiziana Rossetti; Antonio Caprioli; Mumna Al Banchaabouchi; Renato Corradetti; Cornelius Gross
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Science (New York, N.Y.)     Volume:  321     ISSN:  1095-9203     ISO Abbreviation:  Science     Publication Date:  2008 Jul 
Date Detail:
Created Date:  2008-07-07     Completed Date:  2008-07-18     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0404511     Medline TA:  Science     Country:  United States    
Other Details:
Languages:  eng     Pagination:  130-3     Citation Subset:  IM    
Affiliation:
Mouse Biology Unit, European Molecular Biology Laboratory (EMBL), Via Ramarini 32, 00015 Monterotondo, Italy.
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MeSH Terms
Descriptor/Qualifier:
Animals
Autonomic Nervous System / physiology*
Autoreceptors / metabolism
Body Temperature
Doxycycline / pharmacology
Electrocardiography
Feedback, Physiological
Heart Rate
Homeostasis
Humans
Infant
Mice
Mice, Transgenic
Motor Activity
Neural Inhibition*
Neurons / metabolism,  physiology*
Piperazines / administration & dosage,  pharmacology
Pyridines / administration & dosage,  pharmacology
Raphe Nuclei / cytology,  metabolism
Receptor, Serotonin, 5-HT1A / genetics,  metabolism
Serotonin / metabolism*
Serotonin Antagonists / administration & dosage,  pharmacology
Sudden Infant Death / etiology*
Sympathetic Nervous System / physiology
Synaptic Transmission
Tryptophan / metabolism,  pharmacology
Grant Support
ID/Acronym/Agency:
MH64948/MH/NIMH NIH HHS
Chemical
Reg. No./Substance:
0/Autoreceptors; 0/Piperazines; 0/Pyridines; 0/Serotonin Antagonists; 112692-38-3/Receptor, Serotonin, 5-HT1A; 146714-97-8/WAY 100635; 50-67-9/Serotonin; 564-25-0/Doxycycline; 73-22-3/Tryptophan
Comments/Corrections
Comment In:
Science. 2008 Nov 7;322(5903):856-7; author reply 856-7   [PMID:  18988825 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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