Pharmacology & Toxicology Poster Session
Lajard, A-M. (CNRS ESA-6034 Marseille, France)
Monteau, R. (CNRS ESA-6034 Marseille, France)
Lanoir, J. (Lab. Neurobiologie CNRS UPR-9024, Marseille, France)
Christolomme, A. (Lab. Neurobiologie CNRS UPR-9024, Marseille, France)
Seif, I. (Institut Curie UMR-177 Orsay, France)
De Maeyer, E. (Institut Curie UMR-177 Orsay, France)
Hilaire, G. (Lab. Neurobiologie et Mouvements, CNRS UPR-9011 Marseille, France)
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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|Bou, C.; Lajard, A-M.; Monteau, R.; Lanoir, J.; Christolomme, A.; Seif, I.; De Maeyer, E.; Hilaire, G.; (1998). Serotonin Plays a Crucial Role in the Maturation of Mammalian Central Respiratory Network. Presented at INABIS '98 - 5th Internet World Congress on Biomedical Sciences at McMaster University, Canada, Dec 7-16th. Available at URL http://www.mcmaster.ca/inabis98/pharmtox/bou0719/index.html|
|© 1998 Author(s) Hold Copyright|