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Identifikation von Risikogenen für Alkoholabhängigkeit

Das NMDA-Rezeptor-System

The NMDA receptor system: genetic risk factor for alcoholism

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Zusammenfassung

Alkoholabhängigkeit ist eine der häufigsten Suchterkrankungen, die zum Teil durch erbliche Eigenschaften verursacht wird. Dabei tragen mehrere Gene zur Erkrankung bei, wobei jedes beteiligte Gen nur geringen Effekt auf den Phänotyp hat. Neben der Wirkung auf andere Signaltransduktionsmechanismen inhibiert Alkohol spezifisch die NMDA-Signal-Transduktionskaskade, die den exzitatorischen Effekt von Glutamat im Gehirn vermittelt. Die alkoholsensitiven Zielmoleküle umfassen die NMDA-Rezeptoren, nachfolgende Signalmoleküle des glutamatergen Systems, Glutamattransporter und assoziierte regulatorische Proteine. Adaptive Prozesse des glutamatergen Systems während chronischen Alkoholkonsums könnten eine große Rolle für die Entwicklung späterer Entzugserscheinungen spielen. Studien an Kandidatengenen, sowohl Assoziationsstudien als auch tierexperimentelle Studien, sind geeignet, die oligogenen Effekte nachzuweisen und ein wertvolles Instrument für die Erforschung der Alkoholabhängigkeit.

Summary

Alcohol dependence is one of the most common addictive diseases and known to be in part genetically transmitted, based on an oligogenic background in which each gene involved contributes only little to the resulting phenotype. Besides influencing other signal transduction mechanisms, alcohol specifically inhibits the NMDA signaling cascade, which mediates the excitatory effects of glutamate in the brain. Target molecules, sensitive to ethanol, include the NMDA receptors as well as downstream molecules of the glutamatergic system, glutamate transporters, and associated regulatory proteins. Adaptive processes of the glutamatergic system during chronic alcohol consumption may play a major role for later development of reward symptoms. Candidate gene studies, including association studies and animal models, are powerful and sensitive for detecting oligogenic effects and thus imortant to alcoholism research.

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Danksagungen

Diese Arbeit wurde unterstützt durch den Suchtforschungsverbund Baden Württemberg an GS und KM (FKZ 01 EB 0410) sowie das Nationale Genomforschungsnetz II (NGFN II) an GS, KM und AH.

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Authors and Affiliations

  1. Molekulargenetisches Labor, Zentralinstitut für Seelische Gesundheit, Universität Heidelberg, Mannheim

    G. Schumann, C. Saam & J. Treutlein

  2. Klinik für Sucht und Abhängiges Verhalten, Zentralinstitut für Seelische Gesundheit, Universität Heidelberg, Mannheim

    G. Schumann & K. Mann

  3. Universitätsmedizin Berlin, Campus Charité Mitte, Humboldt Universität

    A. Heinz

  4. Molekulargenetisches Labor, Zentralinstitut für seelische Gesundheit, J5, 68159, Mannheim, Deutschland

    G. Schumann

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Schumann, G., Saam, C., Heinz, A. et al. Identifikation von Risikogenen für Alkoholabhängigkeit . Nervenarzt 76, 1355–1362 (2005). https://doi.org/10.1007/s00115-005-1917-6

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