Neuron
Volume 43, Issue 1, 8 July 2004, Pages 43-55
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Article
Expression of Ca2+-Permeable AMPA Receptor Channels Primes Cell Death in Transient Forebrain Ischemia

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Abstract

CA1 pyramidal neurons degenerate after transient global ischemia, whereas neurons in other regions of the hippocampus remain intact. A step in this selective injury is Ca2+ and/or Zn2+ entry through Ca2+-permeable AMPA receptor channels; reducing Ca2+ permeability of AMPA receptors via expression of Ca2+-impermeable GluR2(R) channels or activation of CRE transcription in the hippocampus of adult rats in vivo using shutoff-deficient pSFV-based vectors rescues vulnerable CA1 pyramidal neurons from forebrain ischemic injury. Conversely, the induction of Ca2+ and/or Zn2+ influx through AMPA receptors by expressing functional Ca2+-permeable GluR2(Q) channels causes the postischemic degeneration of hippocampal granule neurons that otherwise are insensitive to ischemic insult. Thus, the AMPA receptor subunit GluR2 gates entry of Ca2+ and/or Zn2+ that leads to cell death following transient forebrain ischemia.

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These authors contributed equally to this work.