HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: fj.07-100743v1 22/7/2340    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Fligny, C. Articles by Vodjdani, G. PubMed PubMed Citation Articles by Fligny, C. Articles by Vodjdani, G.

Maternal serotonin influences cardiac function in adult offspring

Cécile Fligny^*, Yves Fromes, Philippe Bonnin, Michèle Darmon, Elisa Bayard^*, Jean-Marie Launay^||, Francine Côté^*, Jacques Mallet^*,1 and Guilan Vodjdani^*,1

^* Unité Mixte de Recherche 7091 Centre National de la Recherche Scientifique/Université Pierre et Marie Curie, Laboratoire de Génétique Moléculaire de la Neurotransmission et des Processus Neurodégénératifs (LGN),

Institut de Myologie, U582 Institut National de la Santé et de la Recherche Médicale, and

Unité Mixte de Recherche 677 Institut National de la Santé et de la Recherche Médicale/Université Pierre et Marie Curie, Laboratoire de Neuropsychopharmacologie, Hôpital de la Pitié-Salpêtrière, Paris, France; and

Centre de Recherche Cardiovasculaire, Physiologic Explorations Fonctionnelles, U689 Institut National de la Santé et de la Recherche Médicale, Université Denis Diderot, and

^|| Service de Biochimie, Hôpital Lariboisière, APHP, Paris, France

¹Correspondence: UMR 7091 CNRS/UPMC, LGN, Hôpital de la Pitié-Salpêtrière, Bâtiment CERVI, 83 boulevard de l’Hôpital, 75013 Paris, France. E-mail: J.M., mallet{at}chups.jussieu.fr; G.V., vodjdani{at}chups.jussieu.fr

Using the Tph1-invalidated mouse line, in which blood is depleted in serotonin (5-hydroxytryptamine, 5-HT), we have demonstrated previously that maternal 5-HT is required for normal embryonic development. Here, we address the issue of the influence of the maternal 5-HT concentration on the cardiac function of the offspring as adults. We investigated the cardiac phenotype of Tph1-invalidated mice born to Tph1 heterozygous and null mothers. Functionally, all mutants display a significant decrease of cardiac contractility, indicative of impaired left ventricular function. They exhibit progressive dilated cardiomyopathy and are unable to adapt appropriately to a pharmacological stress. Moreover, we show that the cardiopathy is more severe in adult Tph1^–/– mice born to homozygous mothers than to heterozygous mothers. Importantly, the severity of the cardiac phenotype is inversely correlated with the plasma 5-HT concentration but not the whole-blood 5-HT concentration. Thus, plasma 5-HT concentration may be a useful index of heart failure. These findings show that cardiac function, through the plasma 5-HT concentration, is influenced by the maternal serotonergic status.—Fligny, C., Fromes, Y., Bonnin, P., Darmon, M., Bayard, E., Launay, J.-M., Côté, F., Mallet, J., Vodjdani, G. Maternal serotonin influences cardiac function in adult offspring.

Key Words: maternal effect • tryptophan hydroxylase 1-invalidated mouse • heart failure animal model • dilated cardiomyopathy