Document Detail


Arrest of 5HT neuron differentiation delays respiratory maturation and impairs neonatal homeostatic responses to environmental challenges.
MedLine Citation:
PMID:  17656160     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Serotonin (5HT) is a powerful modulator of respiratory circuitry in vitro but its role in the development of breathing behavior in vivo is poorly understood. Here we show, using 5HT neuron-deficient Pet-1 (Pet-1(-/-)) neonates, that serotonergic function is required for the normal timing of postnatal respiratory maturation. Plethysmographic recordings reveal that Pet-1(-/-) mice are born with a depressed breathing frequency and a higher incidence of spontaneous and prolonged respiratory pauses relative to wild type littermates. The wild type breathing pattern stabilizes by postnatal day 4.5, while breathing remains depressed, highly irregular and interrupted more frequently by respiratory pauses in Pet-1(-/-) mice. Analysis of in vitro hypoglossal nerve discharge indicates that instabilities in the central respiratory rhythm generator contribute to the abnormal Pet-1(-/-) breathing behavior. In addition, the breathing pattern in Pet-1(-/-) neonates is susceptible to environmental conditions, and can be further destabilized by brief exposure to hypoxia. By postnatal day 9.5, however, breathing frequency in Pet-1(-/-) animals is only slightly depressed compared to wild type, and prolonged respiratory pauses are rare, indicating that the abnormalities seen earlier in the Pet-1(-/-) mice are transient. Our findings provide unexpected insight into the development of breathing behavior by demonstrating that defects in 5HT neuron development can extend and exacerbate the period of breathing instability that occurs immediately after birth during which respiratory homeostasis is vulnerable to environmental challenges.
Authors:
Jeffery T Erickson; Geoffrey Shafer; Michael D Rossetti; Christopher G Wilson; Evan S Deneris
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2007-06-16
Journal Detail:
Title:  Respiratory physiology & neurobiology     Volume:  159     ISSN:  1569-9048     ISO Abbreviation:  Respir Physiol Neurobiol     Publication Date:  2007 Oct 
Date Detail:
Created Date:  2007-10-01     Completed Date:  2007-12-12     Revised Date:  2014-09-19    
Medline Journal Info:
Nlm Unique ID:  101140022     Medline TA:  Respir Physiol Neurobiol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  85-101     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Animals, Newborn
Anoxia / physiopathology
Cell Differentiation / physiology*
Environmental Exposure
Homeostasis / physiology*
Hypoglossal Nerve / physiology
Immunohistochemistry
Mice
Mice, Mutant Strains
Neurons / cytology*,  metabolism
Plethysmography, Whole Body
Respiration*
Respiratory System / growth & development*,  metabolism
Serotonin / metabolism*
Grant Support
ID/Acronym/Agency:
MH62723/MH/NIMH NIH HHS; R01 MH062723/MH/NIMH NIH HHS; R01 MH062723-02/MH/NIMH NIH HHS; R01 MH062723-03/MH/NIMH NIH HHS; R01 MH062723-04/MH/NIMH NIH HHS; R01 MH062723-05/MH/NIMH NIH HHS; R01 MH062723-05S1/MH/NIMH NIH HHS; R01 MH062723-06/MH/NIMH NIH HHS; R01 MH062723-06S1/MH/NIMH NIH HHS; R01 MH062723-07/MH/NIMH NIH HHS
Chemical
Reg. No./Substance:
333DO1RDJY/Serotonin
Comments/Corrections

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