Growth retardation and altered autonomic control in mice lacking brain serotonin

DOI Web Site 被引用文献16件
  • Natalia Alenina
    Max-Delbrück-Center for Molecular Medicine (MDC), Robert-Rössle-Strasse 10, D-13125 Berlin, Germany; and
  • Dana Kikic
    Max-Delbrück-Center for Molecular Medicine (MDC), Robert-Rössle-Strasse 10, D-13125 Berlin, Germany; and
  • Mihail Todiras
    Max-Delbrück-Center for Molecular Medicine (MDC), Robert-Rössle-Strasse 10, D-13125 Berlin, Germany; and
  • Valentina Mosienko
    Max-Delbrück-Center for Molecular Medicine (MDC), Robert-Rössle-Strasse 10, D-13125 Berlin, Germany; and
  • Fatimunnisa Qadri
    Max-Delbrück-Center for Molecular Medicine (MDC), Robert-Rössle-Strasse 10, D-13125 Berlin, Germany; and
  • Ralph Plehm
    Max-Delbrück-Center for Molecular Medicine (MDC), Robert-Rössle-Strasse 10, D-13125 Berlin, Germany; and
  • Philipp Boyé
    Max-Delbrück-Center for Molecular Medicine (MDC), Robert-Rössle-Strasse 10, D-13125 Berlin, Germany; and
  • Larissa Vilianovitch
    Max-Delbrück-Center for Molecular Medicine (MDC), Robert-Rössle-Strasse 10, D-13125 Berlin, Germany; and
  • Reinhard Sohr
    Institute of Pharmacology, Charité-University Medicine, D-10117 Berlin, Germany
  • Katja Tenner
    Max-Delbrück-Center for Molecular Medicine (MDC), Robert-Rössle-Strasse 10, D-13125 Berlin, Germany; and
  • Heide Hörtnagl
    Institute of Pharmacology, Charité-University Medicine, D-10117 Berlin, Germany
  • Michael Bader
    Max-Delbrück-Center for Molecular Medicine (MDC), Robert-Rössle-Strasse 10, D-13125 Berlin, Germany; and

説明

<jats:p> Serotonin synthesis in mammals is initiated by 2 distinct tryptophan hydroxylases (TPH), TPH1 and TPH2. By genetically ablating TPH2, we created mice ( <jats:italic>Tph2</jats:italic> <jats:sup>−/−</jats:sup> ) that lack serotonin in the central nervous system. Surprisingly, these mice can be born and survive until adulthood. However, depletion of serotonin signaling in the brain leads to growth retardation and 50% lethality in the first 4 weeks of postnatal life. Telemetric monitoring revealed more extended daytime sleep, suppressed respiration, altered body temperature control, and decreased blood pressure (BP) and heart rate (HR) during nighttime in <jats:italic>Tph2</jats:italic> <jats:sup>−/−</jats:sup> mice. Moreover, <jats:italic>Tph2</jats:italic> <jats:sup>−/−</jats:sup> females, despite being fertile and producing milk, exhibit impaired maternal care leading to poor survival of their pups. These data confirm that the majority of central serotonin is generated by TPH2. TPH2-derived serotonin is involved in the regulation of behavior and autonomic pathways but is not essential for adult life. </jats:p>

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