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

Abstract

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.

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Abbreviations

LTP:

Long-term potentiation

MC:

Mineralocorticoid

GC:

Glucocorticoid

CS:

Corticosterone

AMPA:

α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionate

GABA:

γ-Aminobutyric acid

ACSF:

Artificial cerebrospinal fluid

PCL:

Pyramidal cell layer

SR:

Stratum radiatum

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Authors

Contributions

Planned experiments: H.T. and A.T. Performed the Experiments: Y.S., T.M, and T.F. Analyzed data: H.K. and M.S. Wrote the paper: H.T. and A.T. All authors reviewed the manuscript.

Corresponding author

Correspondence to Atsushi Takeda.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

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Tamano, H., Sato, Y., Takiguchi, M. et al. CA1 LTP Attenuated by Corticosterone is Canceled by Effusol via Rescuing Intracellular Zn2+ Dysregulation. Cell Mol Neurobiol 39, 975–983 (2019). https://doi.org/10.1007/s10571-019-00693-5

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Keywords

  • Effusol
  • Juncus effusus
  • Zn2+
  • Corticosterone
  • Hippocampus
  • Stress