Abstract

Introduction

Materials & Methods

Results

Discussion & Conclusion

References

Discussion
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Tg8 mutant mice obtained from C3H mice by disrupting the gene encoding monoamine oxidase-A - the serotonin (5-HT) degradation enzyme - showed very high 5-HT levels at birth. A comparative study was therefore performed on C3H and Tg8 neonates to determine whether the 9-fold increase in 5-HT levels in Tg8 disturbs the maturation of the respiratory network. In Tg8 mice as compared with wild-type mice, we noted that: (1) fetal brainstem respiratory centres and phrenic motoneurons mature at high endogenous 5-HT levels (biochemical approach); (2) at birth, the respiratory activity is very variable, possibly due to abnormal network wiring (electrophysiological approach); (3) the neonatal phrenic motoneurons display more extensive dendritic tree and more numerous dendritic spines (morphological approach); (4) the 5-HT1A modulation of respiratory frequency is present in C3H neonates but lacking in Tg8 neonates (pharmacological approach); (5) the density of the 5-HT1A receptors in the medulla and cervical cord is lower in Tg8 than in C3H neonates ([3H]8-OH-DPAT quantitative autoradiography). To conclude, the abnormally high serotonergic levels present during gestation in Tg8 mice disturb the maturation of both respiratory network and 5-HT modulation. Therefore, as serotonin plays a crucial role in the maturation of the respiratory network, drugs such as serotonin uptake inhibitors or monoamine oxidase inhibitors should be used with caution during pregnancy.

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Poster Number PAbou0719
Keywords: Serotonin, 5-HT1A Receptors, Respiration, Mice ontogenesis, Medullary Network