Inhibition of EphA4 signaling after ischemia-reperfusion reduces apoptosis of CA1 pyramidal neurons
Abstract
Hippocampal CA1 pyramidal neurons are sensitive to ischemic damage. However, the cellular and molecular mechanisms underlying neuronal cell death caused by ischemia-reperfusion (I/R) are not completely clear. Here, we report that the ephrinA/EphA cell-cell interaction signaling pathway plays an important role in the apoptosis of hippocampal CA1 pyramidal neurons induced by I/R. We found that the expression of ephrinA3 and EphA4 is increased in the CA1 region following transient forebrain ischemia. Blocking ephrinA3/EphA4 interaction by EphA4-Fc, an inhibitor of EphA4, attenuated apoptotic neuronal cell death, likely through the inhibition of caspase-3 activation. These results reveal a novel function of ephrin/Eph signaling in the regulation of apoptosis in CA1 pyramidal neurons after I/R.
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Brain Ischemia
Brain ischemia is a condition in which there is insufficient blood flow to the brain to meet metabolic demand. Discover the latest research on brain ischemia here.
Apoptosis
Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis