Interaction between defects in ventilatory and thermoregulatory control in mice lacking 5-HT neurons

Matthew R Hodges; George B Richerson

doi:10.1016/j.resp.2008.08.003

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Interaction between defects in ventilatory and thermoregulatory control in mice lacking 5-HT neurons

Journal article

Peer reviewed

Interaction between defects in ventilatory and thermoregulatory control in mice lacking 5-HT neurons

Matthew R Hodges and George B Richerson

Respiratory physiology & neurobiology, Vol.164(3), pp.350-357

12/31/2008

DOI: 10.1016/j.resp.2008.08.003

PMCID: PMC2613046

PMID: 18775520

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Abstract

We have previously shown that mice with near-complete absence of 5-HT neurons (Lmx1bf/f/p) display a blunted hypercapnic ventilatory response (HCVR) and impaired cold-induced thermogenesis, but have normal baseline ventilation (), core body temperature (TCore) and hypoxic ventilatory responses (HVR) at warm ambient temperatures (TAmb; 30 degrees C). These results suggest that 5-HT neurons are an important site for integration of ventilatory, metabolic and temperature control. To better define this integrative role, we now determine how a moderate cold stress (TAmb of 25 degrees C) influences ventilatory control in adult Lmx1bf/f/p mice. During whole animal plethysmographic recordings at 25 degreesC, baseline , metabolic rate , and TCore of Lmx1bf/f/p mice were reduced (P < 0.001) compared to wild type (WT) mice. Additionally, the HCVR was reduced in Lmx1bf/f/p mice during normoxic (-33.1%) and hyperoxic (-40.9%) hypercapnia. However, in Lmx1bf/f/p mice was equal to that in WT mice while breathing 10% CO2, indicating that non-5-HT neurons may play a dominant role during extreme hypercapnia. Additionally, ventilation was decreased during hypoxia in Lmx1bf/f/p mice compared to WT mice at 25 degrees C due to decreased TCore. These data suggest that a moderate cold stress in Lmx1bf/f/p mice leads to further dysfunction in ventilatory control resulting from failure to adequately maintain TCore. We conclude that 5-HT neurons contribute to the hypercapnic ventilatory response under physiologic, more than during extreme levels of CO2, and that mild cold stress further compromises ventilatory control in Lmx1bf/f/p mice as a result of defective thermogenesis.

Hypercapnia - physiopathology

Telemetry - methods

Transcription Factors - deficiency

Respiratory Mechanics - genetics

Plethysmography - methods

Mice, Knockout

Pulmonary Ventilation - genetics

Animals

Analysis of Variance

Body Temperature - genetics

Time Factors

Homeodomain Proteins

Neurons - physiology

Female

Hypoxia - physiopathology

LIM-Homeodomain Proteins

Mice

Body Temperature Regulation - genetics

Serotonin - deficiency

Details

Title: Subtitle: Interaction between defects in ventilatory and thermoregulatory control in mice lacking 5-HT neurons
Creators: Matthew R Hodges - Department of Neurology, Yale University School of Medicine, New Haven, CT 06520, United States. matthew.hodges@yale.edu
George B Richerson
Resource Type: Journal article
Publication Details: Respiratory physiology & neurobiology, Vol.164(3), pp.350-357
DOI: 10.1016/j.resp.2008.08.003
PMID: 18775520
PMCID: PMC2613046
NLM abbreviation: Respir Physiol Neurobiol
ISSN: 1569-9048
eISSN: 1878-1519
Publisher: Netherlands
Grant note: R01 HL052539-08 / NHLBI NIH HHS R01 HL052539 / NHLBI NIH HHS HD052772 / NICHD NIH HHS R01 HD052772 / NICHD NIH HHS P01 HD036379 / NICHD NIH HHS R01 HD052772-02 / NICHD NIH HHS P01HD36379 / NICHD NIH HHS
Language: English
Date published: 12/31/2008
Academic Unit: Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Neurosurgery
Record Identifier: 9984020645702771

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