Altered ventilatory and thermoregulatory control in male and female adult Pet-1 null mice

Matthew R Hodges; Simon Best; George B Richerson

doi:10.1016/j.resp.2011.03.020

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Altered ventilatory and thermoregulatory control in male and female adult Pet-1 null mice

Journal article

Peer reviewed

Altered ventilatory and thermoregulatory control in male and female adult Pet-1 null mice

Matthew R Hodges, Simon Best and George B Richerson

Respiratory physiology & neurobiology, Vol.177(2), pp.133-140

07/31/2011

DOI: 10.1016/j.resp.2011.03.020

PMCID: PMC4554716

PMID: 21453797

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https://www.ncbi.nlm.nih.gov/pmc/articles/4554716View

Open Access

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.

Immunohistochemistry

Body Temperature Regulation - physiology

Transcription Factors - deficiency

Medulla Oblongata - metabolism

Male

Neurons - cytology

Sex Characteristics

Mice, Knockout

Transcription Factors - metabolism

Medulla Oblongata - cytology

Animals

Serotonin - metabolism

Pulmonary Ventilation - physiology

Female

Mice

Neurons - metabolism

Plethysmography

Details

Title: Subtitle: Altered ventilatory and thermoregulatory control in male and female adult Pet-1 null mice
Creators: Matthew R Hodges - Departments of Neurology and Cellular & Molecular Physiology, Yale University School of Medicine, New Haven, CT 06520, United States. mhodges@mcw.edu
Simon Best
George B Richerson
Resource Type: Journal article
Publication Details: Respiratory physiology & neurobiology, Vol.177(2), pp.133-140
DOI: 10.1016/j.resp.2011.03.020
PMID: 21453797
PMCID: PMC4554716
NLM abbreviation: Respir Physiol Neurobiol
ISSN: 1569-9048
eISSN: 1878-1519
Publisher: Netherlands
Grant note: R01 HL052539 / NHLBI NIH HHS R01 HD052772 / NICHD NIH HHS P01 HD036379 / NICHD NIH HHS U01 NS090414 / NINDS NIH HHS
Language: English
Date published: 07/31/2011
Academic Unit: Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Neurosurgery
Record Identifier: 9984020770102771

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