GluN2A/B ratio elevation induced by cortical spreading depression: electrophysiological and quantitative studies of the hippocampus
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Cortical spreading depression (CSD), an underlying mechanism of migraine aura, propagates to the hippocampus, and might explain hippocampusassociated symptoms during migraine attack. We hypothesised that this process is, some parts, mediated by NMDA receptors. By using a rat model, CSD was elicited by solid KCl for 45 minutes prior to electrophysiological and quantitative analyses. The result from electrophysiological study was the ratio of glutamate NMDA receptor 2A and 2B subunits (GluN2A/B). Total NMDA receptor response was isolated using an AMPA antagonist, prior to a GluN2B receptor antagonist. The GluN2A/B ratio was calculated by dividing the remaining NMDA-mediated field-excitatory synaptic potentials (fEPSP) with the subtracted difference of NMDAmediated fEPSP. Western blot analysis of the hippocampus was performed to confirm the quantitative change of GluN2A/B ratio. In hippocampal slice study (n = 12), the GluN2A/B ratio of hippocampal fEPSP was significantly increased in CSD group. Western blot analysis (n = 30) revealed an increase in GluN2A subunits and a decrease in GluN2B subunits in the hippocampus ipsilateral to the CSD induction. Our current study revealed that GluN2A/B ratio was shown to be elevated following CSD stimulation by increasing the total number of GluN2A while reducing the total number of GluN2B subunits. This ratio was demonstrated to be associated with synaptic plasticity of the hippocampus in numerous studies. In conclusion, we showed that CSD increased GluN2A/B ratio, in turn, would result in altered synaptic plasticity. Our findings provide a probable implication on the correlation of migraine aura and hippocampusassociated symptoms.
KeywordsNMDA receptors migraine aura transient global amnesia (TGA) hippocampal spreading depression long-term potentiation (LTP) AMPA receptors
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