• Proc. Natl. Acad. Sci. U.S.A. · Aug 2011

    Ineffective erythropoiesis with reduced red blood cell survival in serotonin-deficient mice.

    • Pascal Amireault, Sarah Hatia, Elisa Bayard, Florence Bernex, Corinne Collet, Jacques Callebert, Jean-Marie Launay, Olivier Hermine, Elke Schneider, Jacques Mallet, Michel Dy, and Francine Côté.
    • Faculté de Médecine, Université Paris Descartes, Centre National de la Recherche Scientifique Unité Mixte de Recherche 8147, Hôpital Necker, 75743 Paris Cedex 15, France.
    • Proc. Natl. Acad. Sci. U.S.A. 2011 Aug 9;108(32):13141-6.

    AbstractSerotonin (5-HT) has long been recognized as a neurotransmitter in the central nervous system, where it modulates a variety of behavioral functions. Availability of 5-HT depends on the expression of the enzyme tryptophan hydroxylase (TPH), and the recent discovery of a dual system for 5-HT synthesis in the brain (TPH2) and periphery (TPH1) has renewed interest in studying the potential functions played by 5-HT in nonnervous tissues. Moreover, characterization of the TPH1 knockout mouse model (TPH1(-/-)) led to the identification of unsuspected roles for peripheral 5-HT, revealing the importance of this monoamine in regulating key physiological functions outside the brain. Here, we present in vivo data showing that mice deficient in peripheral 5-HT display morphological and cellular features of ineffective erythropoiesis. The central event occurs in the bone marrow where the absence of 5-HT hampers progression of erythroid precursors expressing 5-HT(2A) and 5-HT(2B) receptors toward terminal differentiation. In addition, red blood cells from 5-HT-deficient mice are more sensitive to macrophage phagocytosis and have a shortened in vivo half-life. The combination of these two defects causes TPH1(-/-) animals to develop a phenotype of macrocytic anemia. Direct evidence for a 5-HT effect on erythroid precursors is provided by supplementation of the culture medium with 5-HT that increases the proliferative capacity of both 5-HT-deficient and normal cells. Our thorough analysis of TPH1(-/-) mice provides a unique model of morphological and functional aberrations of erythropoiesis and identifies 5-HT as a key factor for red blood cell production and survival.

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