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 Ca(2+) and/or Zn(2+) entry through Ca(2+)-permeable AMPA receptor channels; reducing Ca(2+) permeability of AMPA receptors via expression of Ca(2+)-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 Ca(2+) and/or Zn(2+) influx through AMPA receptors by expressing functional Ca(2+)-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 Ca(2+) and/or Zn(2+) that leads to cell death following transient forebrain ischemia.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Animals, Newborn
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Calcium / metabolism
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Calcium Channels / genetics
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Calcium Channels / metabolism*
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Calcium Channels, Q-Type / genetics
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Calcium Channels, Q-Type / metabolism
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Calcium Signaling / genetics*
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Cell Death / genetics
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Cell Membrane Permeability / genetics
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Cyclic AMP Response Element-Binding Protein / genetics
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Cyclic AMP Response Element-Binding Protein / metabolism
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Cyclin-Dependent Kinase 5
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Cyclin-Dependent Kinases / genetics
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Cyclin-Dependent Kinases / metabolism
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Disease Models, Animal
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Hippocampus / metabolism
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Hippocampus / physiopathology
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In Vitro Techniques
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Integrases / genetics
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Integrases / metabolism
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Ion Channel Gating / genetics
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Ischemic Attack, Transient / genetics
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Ischemic Attack, Transient / metabolism*
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Ischemic Attack, Transient / pathology
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Nerve Degeneration / genetics
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Nerve Degeneration / metabolism
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Nerve Degeneration / pathology
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Prosencephalon / metabolism*
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Prosencephalon / pathology
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Protein Binding / genetics
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Pyramidal Cells / metabolism
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Pyramidal Cells / pathology
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Rats
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Rats, Sprague-Dawley
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Receptors, AMPA / genetics
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Receptors, AMPA / metabolism*
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Zinc / metabolism
Substances
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Calcium Channels
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Calcium Channels, Q-Type
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Cyclic AMP Response Element-Binding Protein
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Receptors, AMPA
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Cyclin-Dependent Kinase 5
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Cdk5 protein, rat
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Cyclin-Dependent Kinases
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Cre recombinase
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Integrases
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Zinc
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glutamate receptor ionotropic, AMPA 2
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Calcium