Liu ShuHong, Lau Lorraine, Wei JianShe, Zhu DongYa, Zou Shengwei, Sun Hong-Suo, Fu YangPing, Liu Fang, Lu YouMing
Department of Physiology and Biophysics, Faculty of Medicine, University of Calgary, Calgary T2N 4N1, Canada.
Neuron. 2004 Jul 8;43(1):43-55. doi: 10.1016/j.neuron.2004.06.017.
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.
短暂性全脑缺血后，CA1锥体神经元会发生退化，而海马体其他区域的神经元则保持完整。这种选择性损伤的一个步骤是Ca(2+)和/或Zn(2+)通过Ca(2+)通透的AMPA受体通道进入细胞；在成年大鼠体内，通过表达Ca(2+)不通透的GluR2(R)通道降低AMPA受体的Ca(2+)通透性，或使用基于pSFV的关闭缺陷型载体激活海马体中的CRE转录，可使易损的CA1锥体神经元从前脑缺血损伤中获救。相反，通过表达功能性Ca(2+)通透的GluR2(Q)通道诱导Ca(2+)和/或Zn(2+)通过AMPA受体流入，会导致海马颗粒神经元在缺血后发生退化，而这些神经元原本对缺血损伤不敏感。因此，AMPA受体亚基GluR2控制着Ca(2+)和/或Zn(2+)的进入，这会导致短暂性前脑缺血后细胞死亡。
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