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Extrasynaptic NMDA Receptors : Mediators of Excitotoxic Cell Death

Wittmann, Malte and Bengtson, C. Peter and Bading, Hilmar

In: Krieglstein, J., Klumpp, S. (Hrsg.): Pharmacology of Cerebral Ischemia. Medpharm Scientific Publishers, Stuttgart 2004, pp. 253-266

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Abstract

The N-methyl-D-aspartate (NMDA) type of glutamate receptor is a calcium-permeable ion channel with important functions in the physiology and pathology of the mammalian brain. NMDA receptors are critical for long-lasting, activity-induced changes in synaptic transmission, a process thought to be involved in learning and memory. NMDA receptors also control neuronal survival and cell death. How can the biological consequences of NMDA receptor activation be so diametrically opposed? The outcome of NMDA receptor activation appears to be determined by its localization. Stimulation of synaptic NMDA receptors (by synaptically-released glutamate) activates gene expression mediated by the transcription factor, cAMP-response element-binding-protein (CREB) and induces pro-survival events. In contrast, calcium flux through extrasynaptic NMDA receptors overrides these functions, shutting off CREB activity, and causing mitochondrial dysfunction and cell death. These differences in the biological response are likely due to differences in the intracellular signaling complexes associated with synaptic vs. extrasynaptic NMDA receptors. As extrasynaptic NMDA receptors are thought to be activated following hypoxic/ischemic insults, specific blockade of extrasynaptic NMDA receptors or its signaling complex may efficiently reduce neuron loss following stroke.

Item Type: Book Section
Editors: Krieglstein, J., Klumpp, S.
Title of Book: Pharmacology of Cerebral Ischemia
Publisher: Medpharm Scientific Publishers
Place of Publication: Stuttgart
Date Deposited: 21 Mar 2005 13:55
Date: 2004
Page Range: pp. 253-266
Faculties / Institutes: Service facilities > Interdisziplinäres Zentrum für Neurowissenschaften
Subjects: 570 Life sciences
Controlled Keywords: NMDA receptor, calcium signaling, survival, cell death, CREB, stroke
Uncontrolled Keywords: NMDA receptor , calcium signaling , survival , cell death , CREB , stroke
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