CA1 LTP Attenuated by Corticosterone is Canceled by Effusol via Rescuing Intracellular Zn²⁺ Dysregulation

Exposure to corticosterone attenuates hippocampal CA1 long-term potentiation (LTP) via intracellular Zn²⁺ dysregulation. Here we report that effusol, a phenanthrene isolated from Chinese medicine Juncus effusus, rescues CA1 LTP attenuated by corticosterone. In vivo microdialysis experiment indicated that both increases in extracellular glutamate induced under perfusion with corticosterone and high K⁺ are suppressed in the hippocampus by co-perfusion with effusol. Because corticosterone and high K⁺ also increase extracellular Zn²⁺ level, followed by intracellular Zn²⁺ dysregulation, the effect of effusol on both the increases was examined in brain slice experiments. Effusol did not suppress increase in extracellular Zn²⁺ in the hippocampal CA1 of brain slices bathed in corticosterone, but suppressed increase in intracellular Zn²⁺, which may be linked with suppressing the increase in extracellular glutamate in vivo. In vivo CA1 LTP was attenuated under perfusion with corticosterone prior to LTP induction, while the attenuation was rescued by co-perfusion with effusol, suggesting that the rescuing effect of effusol is due to suppressing the increase in intracellular Zn²⁺ in CA1 pyramidal cells. The present study indicates that CA1 LTP attenuated by corticosterone is canceled by effusol, which rescues intracellular Zn²⁺ dysregulation via suppressing extracellular glutamate accumulation. It is likely that effusol defends the hippocampal function against stress-induced cognitive decline.