title: Altered ventilatory and thermoregulatory control in male and female adult Pet-1 null mice.
abstract: 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.
authors: Departments of Neurology and Cellular & Molecular Physiology, Yale University School of Medicine, New Haven, CT 06520, United States. mhodges@mcw.edu
authors: Matthew R
authors: MR
authors: Hodges
authors: Simon
authors: S
authors: Best
authors: George B
authors: GB
authors: Richerson
mesh_terms: D000818:Animals; D001833:Body Temperature Regulation / Q000502:physiology*; D005260:Female; D007150:Immunohistochemistry; D008297:Male; D008526:Medulla Oblongata / Q000166:cytology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D010991:Plethysmography; D012123:Pulmonary Ventilation / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism; D012727:Sex Characteristics; D014157:Transcription Factors / Q000172:deficiency / Q000378:metabolism*
chemical_list: C484684:Fev protein, mouse; D014157:Transcription Factors; D012701:Serotonin