Altered ventilatory and thermoregulatory control in male and female adult Pet-1 null mice. Respir Physiol Neurobiol 2011 Jul 31;177(2):133-40
Date
04/02/2011Pubmed ID
21453797Pubmed Central ID
PMC4554716DOI
10.1016/j.resp.2011.03.020Scopus ID
2-s2.0-79957439144 (requires institutional sign-in at Scopus site) 40 CitationsAbstract
The integrity of the serotonin (5-HT) system is essential to normal respiratory and thermoregulatory control. Male and female transgenic mice lacking central 5-HT neurons (Lmx1b(f/f/p) mice) show a 50% reduction in the hypercapnic ventilatory response and insufficient heat generation when cooled (Hodges and Richerson, 2008a; Hodges et al., 2008b). Lmx1b(f/f/p) mice also show reduced body temperatures (T(body)) and O(2) consumption [Formula: see text] , and breathe less at rest and during hypoxia and hypercapnia when measured below thermoneutrality (24 °C), suggesting a role for 5-HT neurons in integrating ventilatory, thermal and metabolic control. Here, the hypothesis that Pet-1 null mice, which retain 30% of central 5-HT neurons, will demonstrate similar deficits in temperature and ventilatory control was tested. Pet-1 null mice had fewer medullary tryptophan hydroxylase-immunoreactive (TPH(+)) neurons compared to wild type (WT) mice, particularly in the midline raphé. Female (but not male) Pet-1 null mice had lower baseline ventilation (V(E)), breathing frequency (f), [Formula: see text] and T(body) relative to female WT mice (P < 0.05). In addition, V(E) and [Formula: see text] were decreased in male and female Pet-1 null mice during hypoxia and hypercapnia (P < 0.05), but only male Pet-1 null mice showed a significant deficit in the hypercapnic ventilatory response when expressed as % of control (P < 0.05). Finally, male and female Pet-1 null mice showed significant decreases in T(body) when externally cooled to 4 °C. These data demonstrate that a moderate loss of 5-HT neurons leads to a modest attenuation of mechanisms defending body temperature, and that there are gender differences in the contributions of 5-HT neurons to ventilatory and thermoregulatory control.
Author List
Hodges MR, Best S, 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
AnimalsBody Temperature Regulation
Female
Immunohistochemistry
Male
Medulla Oblongata
Mice
Mice, Knockout
Neurons
Plethysmography
Pulmonary Ventilation
Serotonin
Sex Characteristics
Transcription Factors
