Abstract
Transient, severe forebrain or global ischemia leads to delayed cell death of pyramidal neurons in the hippocampal CA1. The precise molecular mechanisms underlying neuronal cell death after ischemia are as yet unknown. Ca2+ permeable GluR2 lacking alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionate (AMPA) receptors are implicated in the pathogenesis of ischemia-induced degeneration. Global ischemia leads to reduced expression of GluR2 mRNA in vulnerable CAl neurons prior to the delayed cell death. After ischemia, AMPA-receptormediated excitatory postsynaptic currents at the CA1/Schaffer collateral synapse are enhanced and increased in sensitivity to channel blockers selective for Ca2+ permeable AMPA receptors. Moreover, 2,3-dihydroxy-6-nitro-7-sulfamayl-benzo(F)-quinoxaline (NBQX), an AMPA antagonist, protects CA1 neurons against ischemiainduced damage, even when administered 16–24 h after ischemia. These observations suggest that “switching off” GluR2 expression in CAI after an ischemic insult is translated into formation of new AMPA receptors lacking the GluR2 subunit. This change in receptor composition increases AMPA-receptor-mediated Ca2+ entry in response to endogenous glutamate and enhances glutamate pathogenicity in this region (the GluR2 hypothesis). The present study was performed to test whether GluR2 downregulation leads to AMPA-receptor-gated Ca2+ entry into CA1 neurons.
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© 1999 Springer-Verlag Berlin Heidelberg
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Gorter, J.A., Aronica, E.M., Opitz, T., Bennett, M.V.L., Connor, J.A., Zukin, R.S. (1999). Global Ischemia Induces Downregulation of GIuR2 mRNA and Increases AMPA Receptor-Mediated Ca2+ Influx in Hippocampal CA1 Neurons. In: Ito, U., Fieschi, C., Orzi, F., Kuroiwa, T., Klatzo, I. (eds) Maturation Phenomenon in Cerebral Ischemia III. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-58602-6_41
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DOI: https://doi.org/10.1007/978-3-642-58602-6_41
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-540-65023-2
Online ISBN: 978-3-642-58602-6
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