| Arrest of 5HT neuron differentiation delays respiratory maturation and impairs neonatal homeostatic responses to environmental challenges. | |
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MedLine Citation:
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PMID: 17656160 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Jeffery T Erickson; Geoffrey Shafer; Michael D Rossetti; Christopher G Wilson; Evan S Deneris |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2007-06-16 |
Journal Detail:
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Title: Respiratory physiology & neurobiology Volume: 159 ISSN: 1569-9048 ISO Abbreviation: Respir Physiol Neurobiol Publication Date: 2007 Oct |
Date Detail:
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Created Date: 2007-10-01 Completed Date: 2007-12-12 Revised Date: 2012-04-24 |
Medline Journal Info:
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Nlm Unique ID: 101140022 Medline TA: Respir Physiol Neurobiol Country: Netherlands |
Other Details:
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Languages: eng Pagination: 85-101 Citation Subset: IM |
Affiliation:
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Case Western Reserve University School of Medicine, Department of Neurosciences, 10900 Euclid Avenue, Cleveland, OH 44106, USA. erickson@tcnj.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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:
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50-67-9/Serotonin |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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