Skip to main content
SpringerLink
Log in

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

  • Original Research
  • Published:
Cellular and Molecular Neurobiology Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

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

References

  • Dorey R, Piérard C, Shinkaruk S, Tronche C, Chauveau F, Baudonnat M, Béracochéa D (2011) Membrane mineralocorticoid but not glucocorticoid receptors of the dorsal hippocampus mediate the rapid effects of corticosterone on memory retrieval. Neuropsychopharmacology 36:2639–2649

    Article  CAS  Google Scholar 

  • Frederickson CJ, Koh JY, Bush AI (2005) The neurobiology of zinc in health and disease. Nat Rev Neurosci 6:449–462

    Article  CAS  Google Scholar 

  • Greca MD, Fiorentino A, Molinaro A, Monaco P, Previtera L (1993) A bioactive dihydrodibenzoxepin from Juncus effusus. Phytochemistry 34:1182–1184

    Article  Google Scholar 

  • Greca MD, Fiorention A, Monaco P, Previtera L (1994) Cycloartane triterpenes from Juncus effusus. Phytochemistry 35:1017–1022

    Article  Google Scholar 

  • Greca MD, Fiorentino A, Monaco P, Pinto G, Pollio A, Previtera L (1996) Action of antialgal compounds from Juncus effusus L. on Selenastrum capricornutum. J Chem Ecol 22:587–603

    Article  CAS  Google Scholar 

  • Hirano T, Kikuchi K, Urano Y, Nagano T (2002) Improvement and biological applications of fluorescent probes for zinc, ZnAFs. J Am Chem Soc 124:6555–6562

    Article  CAS  Google Scholar 

  • Joëls M, de Kloet ER (2017) The brain mineralocorticoid receptor: a saga in three episodes. J Endocrinol 234:T49–T66

    Article  Google Scholar 

  • Joëls M, Karst H, DeRijk R, de Kloet ER (2008) The coming out of the brain mineralocorticoid receptor. Trends Neurosci 31:1–7

    Article  Google Scholar 

  • Karst H, Berger S, Turiault M, Tronche F, Schutz G, Joels M (2005) Mineralocorticoid receptors are indispensable for nongenomic modulation of hippocampal glutamate transmission by corticosterone. Proc Natl Acad Sci USA 102:19204–19207

    Article  CAS  Google Scholar 

  • Khaksari M, Rashidy-Pour A, Vafaei AA (2007) Central mineralocorticoid receptors are indispensable for corticosterone-induced impairment of memory retrieval in rats. Neuroscience 149:729–738

    Article  CAS  Google Scholar 

  • Kim JJ, Diamond DM (2002) The stressed hippocampus, synaptic plasticity and lost memories. Nat Rev Neurosci 3:453–462

    Article  CAS  Google Scholar 

  • Kim J, Yoon KS (1998) Stress: metaplastic effects in the hippocampus. Trends Neurosci 21:505–509

    Article  CAS  Google Scholar 

  • Kwak S, Weiss JH (2006) Calcium-permeable AMPA channels in neurodegenerative disease and ischemia. Curr Opin Neurobiol 16:281–287

    Article  CAS  Google Scholar 

  • Liao YJ, Zhai HF, Zhang B, Duan TX, Huang JM (2011) Anxiolytic and sedative effects of dehydroeffusol from Juncus effusus in mice. Planta Med 77:416–420

    Article  CAS  Google Scholar 

  • Lynch MA (2004) Long-term potentiation and memory. Physiol Rev 84:87–136

    Article  CAS  Google Scholar 

  • McEwen BS, Sapolsky RM (1995) Stress and cognitive function. Curr Opin Neurobiol 5:205–216

    Article  CAS  Google Scholar 

  • McEwen BS, Bowles NP, Gray JD, Hill MN, Hunter RG, Karatsoreos IN, Nasca C (2015) Mechanisms of stress in the brain. Nat Neurosci 18:1353–1363

    Article  CAS  Google Scholar 

  • Olijslagers JE, De Kloet ER, Elgersma Y, Van Woerden GM, Joëls M, Karst K (2008) Rapid changes in hippocampal CA1 pyramidal cell function via pre- as well as postsynaptic membrane mineralocorticoid receptors. Eur J Neurosci 27:2542–2550

    Article  CAS  Google Scholar 

  • Sajadi AA, Samaei SA, Rashidy-Pour A (2006) Intra-hippocampal microinjections of anisomycin did not block glucocorticoid-induced impairment of memory retrieval in rats: an evidence for non-genomic effects of glucocorticoids. Behav Brain Res 173:158–162

    Article  CAS  Google Scholar 

  • Sandi C (2011) Glucocorticoids act on glutamatergic pathways to affect memory processes. Trends Neurosci 34:165–176

    Article  CAS  Google Scholar 

  • Shima K, Toyota M, Asakawa Y (1991) Phenanthrene derivatives from the medullae of Juncus effusus. Phytochemistry 30:3149–3151

    Article  CAS  Google Scholar 

  • Sindreu CB, Varoqui H, Erickson JD, Perez-Clausell J (2003) Boutons containing vesicular zinc define a subpopulation of synapses with low AMPAR content in rat hippocampus. Cereb Cortex 13:823–829

    Article  Google Scholar 

  • Singhuber J, Baburin I, Khom S, Zehl M, Urban E, Hering S, Kopp B (2012) GABA(A) receptor modulators from the Chinese herbal drug Junci Medulla—the pith of Juncus effusus. Planta Med 78:455–458

    Article  CAS  Google Scholar 

  • Suh SW, Jo SM, Vajda Z, Danscher G (2001) Adrenalectomy causes loss of zinc ions in zinc-enriched (ZEN) terminals and decreases seizure-induced neuronal death. Brain Res 895:25–32

    Article  CAS  Google Scholar 

  • Suzuki M, Sato Y, Tamura K, Tamano H, Takeda A (2018) Rapid intracellular Zn2+ dysregulation via membrane corticosteroid receptor activation affects in vivo CA1 LTP. Mol Neurobiol. https://doi.org/10.1007/s12035-018-1159-9

    Article  PubMed  Google Scholar 

  • Takeda A, Fuke S, Tsutsumi W, Oku N (2007) Negative modulation of presynaptic activity by zinc released from Schaffer collaterals. J Neurosci Res 85:3666–3672

    Article  CAS  Google Scholar 

  • Takeda A, Ando M, Kanno S, Oku N (2009) Unique response of zinc in the hippocampus to behavioral stress and attenuation of subsequent mossy fiber long-term potentiation. NeuroToxicology 30:712–717

    Article  CAS  Google Scholar 

  • Takeda A, Takada S, Nakamura M, Suzuki M, Tamano H, Ando M, Oku N (2011) Transient increase in Zn2+ in hippocampal CA1 pyramidal neurons causes reversible memory deficit. PLoS ONE 6:e28615

    Article  CAS  Google Scholar 

  • Takeda A, Suzuki M, Tamano H, Takada S, Ide K, Oku K (2012) Involvement of glucocorticoid-mediated Zn2+ signaling in attenuation of hippocampal CA1 LTP by acute stress. Neurochem Int 60:394–399

    Article  CAS  Google Scholar 

  • Takeda A, Koike Y, Osawa M, Tamano H (2018a) Characteristic of extracellular Zn2+ influx in the middle-aged dentate gyrus and its involvement in attenuation of LTP. Mol Neurobiol 55:2185–2195

    Article  CAS  Google Scholar 

  • Takeda A, Tamano H, Hisatsune M, Murakami T, Nakada H, Fujii H (2018b) Maintained LTP and memory are lost by Zn2+ influx into dentate granule cells, but not Ca2+ influx. Mol Neurobiol 55:1498–1508

    Article  CAS  Google Scholar 

  • Wang Y, Wang Y, Zhai H, Liao Y, Zhang B, Huang J (2012) Phenanthrenes from Juncus effusus with anxiolytic and sedative activities. Nat Prod Res 26:1234–1239

    Article  CAS  Google Scholar 

  • Weiss JH (2011) Ca permeable AMPA channels in diseases of the nervous system. Front Mol Neurosci 4:42

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurophysiology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526, Japan

    Haruna Tamano, Yuichi Sato, Mako Takiguchi, Taku Murakami, Miki Suzuki & Atsushi Takeda

  2. Satoen CO., LTD, 1057 Ohhara, Aoi-ku, Shizuoka, 421-1392, Japan

    Toshiyuki Fukuda

  3. Research Institute of Green Science and Technology, Shizuoka University, 836 Ohya, Suruga-ku, Shizuoka, 422-8529, Japan

    Hirokazu Kawagishi

Authors
  1. Haruna Tamano
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yuichi Sato
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mako Takiguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Taku Murakami
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Toshiyuki Fukuda
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hirokazu Kawagishi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Miki Suzuki
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Atsushi Takeda
    View author publications

    You can also search for this author in PubMed Google Scholar

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.

Ethics declarations

Conflict of interest

All authors have no conflict of interest.

Ethical Approval

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

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10571-019-00693-5

Keywords

Search

Navigation