Interaction between defects in ventilatory and thermoregulatory control in mice lacking 5-HT neurons. Respir Physiol Neurobiol 2008 Dec 31;164(3):350-7
Date
09/09/2008Pubmed ID
18775520Pubmed Central ID
PMC2613046DOI
10.1016/j.resp.2008.08.003Scopus ID
2-s2.0-56449121657 (requires institutional sign-in at Scopus site) 42 CitationsAbstract
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.
Author List
Hodges MR, Richerson GBAuthor
Matthew R. Hodges PhD Professor in the Physiology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Analysis of VarianceAnimals
Body Temperature
Body Temperature Regulation
Female
Homeodomain Proteins
Hypercapnia
Hypoxia
LIM-Homeodomain Proteins
Mice
Mice, Knockout
Neurons
Plethysmography
Pulmonary Ventilation
Respiratory Mechanics
Serotonin
Telemetry
Time Factors
Transcription Factors
