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Fortschr Neurol Psychiatr 2003; 71: 36-44
DOI: 10.1055/s-2003-40504
Originalarbeit
© Georg Thieme Verlag Stuttgart · New York

Exzitatorische Neurotransmission bei chronischem Alkoholismus

Excitatory Neurotransmission in AlcoholismS.  Bleich1 , W.  Sperling1 , J.  Wiltfang1 , J.  M.  Maler1 , J.  Kornhuber1
  • 1Klinik mit Poliklinik für Psychiatrie und Psychotherapie, Friedrich-Alexander-Universität zu Erlangen-Nürnberg
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Publication History

Publication Date:
08 July 2003 (online)

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Zusammenfassung

Glutamat ist der wichtigste erregende Neurotransmitter im zentralen Nervensystem. Unter bestimmten Bedingungen wirken Glutamat und weitere exzitatorische Aminosäuren (z. B. Homocystein) toxisch, indem es über Aktivierung spezifischer Glutamatrezeptoren zu akutem oder auch chronischem Nervenzelluntergang führt. Chronische Exposition gegenüber hohen Dosen an Ethanol bewirkt eine Inhibition der glutamatergen Neurotransmission und konsekutiv eine Hochregulierung des N-Methyl-D-Aspartat(NMDA)-Rezeptorproteins, einen Anstieg an mRNA-funktioneller Rezeptoruntereinheiten und eine verstärkte Rezeptorfunktion. Chronischer Alkoholismus ist mit Störungen im Bereich der exzitatorischen Aminosäuren assoziiert. Unter den Bedingungen des Alkoholentzuges treffen pathologisch erhöhte exzitatorische Aminosäuren (z. B. Homocystein) auf vermehrt exprimierte NMDA-Rezeptoren und bewirken durch Agonismus an den Bindungsstellen der NMDA-Rezeptoren eine überschießende glutamaterge Neurotransmission. Diese Alkoholimus-assoziierten pathophysiologischen Umstände könnten Alkoholentzugsanfälle sowie Mechanismen der Exzitotoxizität induzieren. Weiterhin kann die NMDA-vermittelte Verstärkung exzitatorischer Neurotransmission als wichtiger neuroadaptiver Prozess angesehen werden, der das exzitatorische Syndrom beim Alkoholentzug verursacht. Im Folgenden sollen die wichtigsten Bedeutungen der glutamatergen Neurotransmission für Neurotoxizität und Exzitotoxizität beim chronischen Alkoholismus dargestellt werden.

Abstract

Glutamate is the neurotransmitter at the majority of excitatory synapses in the mammalian CNS. It has been proposed that neurotoxicity linked to chronic alcoholism is mediated primarily by activation of glutamate N-methyl-D-aspartate (NMDA) receptors. Since ethanol stabilizes the membrane potential of NMDA receptors a persistent attenuation of glutamatergic neurotransmission occurs in chronic alcoholism resulting in a compensatory up-regulation of NMDA receptors. Thus, delayed neurotoxicity can be triggered by rebound activation of NMDA receptor-mediated neurotransmission during the withdrawal state. Besides glutamate, homocysteine and excitatory amino acids (EAA) have been shown to act as endogenous agonists at the NMDA receptor and increase excitatory postsynaptic potentials. There is evidence that chronic alcoholism is associated with a derangement in this sulfur amino acid metabolism. These findings indicate the role of hyperhomocysteinemia for withdrawal symptoms, the withdrawal state, and alcoholism-associated brain atrophy. The role of alcoholism-associated hyperhomocysteinemia in respect to NMDA-receptor mediated neurotoxicity and excitotoxicity is discussed.

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PD Dr. med. Stefan Bleich

Friedrich-Alexander-Universität zu Erlangen-Nürnberg · Klinik mit Poliklinik für Psychiatrie und Psychotherapie

Schwabachanlage 6 - 10

91054 Erlangen

Email: stefan.bleich@psych.imed.uni.erlangen.de

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