Interaction between defects in ventilatory and thermoregulatory control in mice lacking 5-HT neurons.
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.
Hodges
Matthew R
MR
Department of Neurology, Yale University School of Medicine, New Haven, CT 06520, United States. matthew.hodges@yale.edu
Richerson
George B
GB
D000704:Analysis of Variance; D000818:Animals; D001831:Body Temperature / Q000235:genetics; D001833:Body Temperature Regulation / Q000235:genetics*; D005260:Female; D018398:Homeodomain Proteins; D006935:Hypercapnia / Q000503:physiopathology; D000860:Hypoxia / Q000503:physiopathology; D060850:LIM-Homeodomain Proteins; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000502:physiology*; D010991:Plethysmography / Q000379:methods; D012123:Pulmonary Ventilation / Q000235:genetics*; D015656:Respiratory Mechanics / Q000235:genetics*; D012701:Serotonin / Q000172:deficiency*; D013686:Telemetry / Q000379:methods; D013997:Time Factors; D014157:Transcription Factors / Q000172:deficiency
D018398:Homeodomain Proteins; C112149:LIM homeobox transcription factor 1 beta; D060850:LIM-Homeodomain Proteins; D014157:Transcription Factors; D012701:Serotonin
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