論文

査読有り
2018年6月8日

Rapid Intracellular Zn2+ Dysregulation via Membrane Corticosteroid Receptor Activation Affects In Vivo CA1 LTP

Molecular Neurobiology
  • Miki Suzuki
  • ,
  • Yuichi Sato
  • ,
  • Kotaro Tamura
  • ,
  • Haruna Tamano
  • ,
  • Atsushi Takeda

開始ページ
1
終了ページ
10
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1007/s12035-018-1159-9
出版者・発行元
Humana Press Inc.

Involvement of membrane mineralocorticoid (MC) and glucocorticoid (GC) receptors in synaptic Zn2+ dynamics remains unclear. Here, we tested whether synaptic plasticity is affected by rapid intracellular Zn2+ dysregulation via membrane MC and GC receptor activation, in comparison with intracellular Ca2+ dysregulation. In anesthetized rats, extracellular Zn2+ level was increased under local perfusion of the hippocampal CA1 with 500 ng/ml corticosterone. In vivo CA1 long-term potentiation (LTP) at Schaffer collateral-CA1 pyramidal cell synapses was attenuated by the pre-perfusion with corticosterone prior to tetanic stimulation, and the attenuation was canceled by co-perfusion with CaEDTA, an extracellular Zn2+ chelator, suggesting that corticosterone-induced increase in extracellular Zn2+ is involved in the subsequent attenuation of LTP. In rat brain slices, corticosterone-induced increases in extracellular and intracellular Zn2+ were blocked in the presence of spironolactone, a MC receptor antagonist that canceled corticosterone-induced attenuation of LTP. Mifepristone, a GC receptor antagonist, which canceled corticosterone-induced attenuation of LTP, also blocked corticosterone-induced increase in intracellular Zn2+, but not extracellular Zn2+. Moreover, corticosterone-induced decrease in phosphorylated CaMKII was restored in the presence of CaEDTA or spironolactone. These results indicate that glucocorticoid rapidly induces the increase in intracellular Zn2+, which occurs via membrane MC and GC receptor activations, and decreases phosphorylated CaMKII level, resulting in attenuating LTP. Membrane MC and GC receptors induce intracellular Zn2+ dysregulation via differential mechanisms. In contrast, glucocorticoid-induced intracellular Ca2+ dysregulation is not crucial for affecting LTP.

リンク情報
DOI
https://doi.org/10.1007/s12035-018-1159-9
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/29948940

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