Premium
Neonatal mice lacking serotonin neurons have high mortality that is worsened on exposure to hypoxia and hypercapnia.
Author(s) -
Cerpa Veronica E,
Flynn Rachel,
Jamison Rachel,
Richerson George B
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.613.10
Subject(s) - hypercapnia , hypoxia (environmental) , hyperoxia , medicine , respiratory system , endocrinology , serotonin , biology , chemistry , lung , oxygen , organic chemistry , receptor
Lmx1b f/f/p mice, which selectively lack central serotonin (5‐HT) neurons, have respiratory abnormalities, high mortality and growth retardation in the perinatal period. Here we studied the effects on mortality and growth rate of raising neonatal WT and Lmx1b f/f/p mice from ages P0‐P21 in environments containing 21% O 2 , 10% O 2 , 10% O 2 & 5% CO 2 or 50% O 2 . Lmx1b f/f/p mice had lower growth rate compared to WT in the same gas condition. Interestingly, WT mice raised in hypoxia grew at a rate equivalent to Lmx1b f/f/p mice raised in normoxia, whereas hypoxia further reduced growth of Lmx1b f/f/p mice. ANOVA revealed a significant effect of age (p < 0.001) and gas conditions (p < 0.001). Moreover, there was high perinatal mortality of Lmx1b f/f/p mice in normoxia that was worsened by hypoxia and improved by hyperoxia. The expected Mendelian ratio of the two genotypes (KO/WT) at the time litters were discovered should have been 1, but it was 0.48 in normoxia, 0.29 in hypoxia, 0.55 in hypoxic‐hypercapnia and 1.54 in hyperoxia. Kaplan‐Meier curves showed continued excess mortality in Lmx1b f/f/p mice for the first 3 postnatal days. Postnatal mortality was also worsened with hypoxia and improved with hyperoxia. Our results indicate that a defect in the 5‐HT system creates heightened vulnerability to hypoxia in neonatal mice, which could be related to the ventilatory abnormalities and vulnerability to exogenous stressors of SIDS infants.