期刊
JOURNAL OF PHYSIOLOGY-LONDON
卷 586, 期 9, 页码 2321-2329出版社
WILEY
DOI: 10.1113/jphysiol.2008.152231
关键词
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资金
- NHLBI NIH HHS [R37 HL028066, R37 HL 28066] Funding Source: Medline
Medullary serotonergic (5-HT) neurons are implicated in central chemoreception and 5-HT abnormalities are present in many cases of the sudden infant death syndrome (SIDS). Mice with a targeted disruption of the serotonin transporter (5-HTT) develop in the presence of excess 5-HT in brain extracellular fluid (ECF). As adults they exhibit reduced 5-HT neuron activity and 5-HT1A receptor binding with varying changes in postsynaptic 5-HT receptor function. They exhibit behavioural phenotypes (anxiety, reduced aggression) but little is known about their control of breathing. We show that conscious adult male and female 5-HTT knockout mice breathing air at room temperature have a higher resting. V-O2, breathing frequency and V-E but a normal body temperature and V-E/V-O2 ratio (the ventilatory equivalent) compared to wild-type (WT) controls. In hypercapnia, there is a reduced ventilatory response (expressed as the V-E/V-O2 ratio) that is much more prominent in males (-68%) than females (-22%). In hypoxia, both males and females exhibit a higher V-E, V-O2 and body temperature but their. V-E/V-O2 ratio is normal. We conclude that 5-HTT knockout mice have a diminished function of the medullary 5-HT system, which is manifest most remarkably in a substantial loss of CO2 sensitivity predominantly in males. This finding supports the importance of medullary 5-HT neurons in central chemoreception. Females either rely less on 5-HT neurons in chemoreception or adapt more readily to the loss of 5-HT function. This genetic model allows examination of the role of excess 5-HT in ECF in the development of the control of breathing and central chemoreception, which may be pertinent to SIDS.
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