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.
journal_name
Respir Physiol Neurobioljournal_title
Respiratory physiology & neurobiologyauthors
Hodges MR,Richerson GBdoi
10.1016/j.resp.2008.08.003subject
Has Abstractpub_date
2008-12-31 00:00:00pages
350-7issue
3eissn
1569-9048issn
1878-1519pii
S1569-9048(08)00217-6journal_volume
164pub_type
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