Neurochemical Research

, Volume 33, Issue 5, pp 776–783 | Cite as

Promotion of Neuronal Plasticity by (−)-Epigallocatechin-3-Gallate

  • Wen Xie
  • Narayan Ramakrishna
  • Andrzej Wieraszko
  • Yu-Wen Hwang
Original paper


The consumption of (−)-epigallocatechin-3-gallate (EGCG), the major polyphenolic compound found in green tea, has been associated with various neurological benefits including cognitive improvement. The physiological basis for this effect is unknown. In this study, we used synaptic transmission between the CA3 and CA1 regions (Schaffer collateral) of the mouse hippocampus to examine the effects of EGCG on neuronal plasticity. We found that the level of high frequency stimulation-evoked long-term potentiation (LTP) was significantly enhanced when hippocampal slices were pre-incubated with 10 μM EGCG for 1 h prior to the experiment. EGCG incubation also enabled hippocampal slices prepared from Ts65Dn mice, a Down syndrome mouse model deficient in LTP, to express LTP to a level comparable to the normal controls. EGCG treatment did not alter the degree of pair-pulse inhibition; therefore, the enhancement effect of EGCG is unlikely to involve the attenuation of this inhibitory mechanism.


LTP EGCG Ts65Dn mouse Down syndrome animal model Paired-pulse inhibition Tea catechins Hippocampal slices 



We thank Drs. David Miller, Tatyana Adayev, Sarah Nolin, Carl Dobkin, Robert Denman, and Ms. Maureen Marlow for critical reading of this manuscript. This work was supported in part by the New York State Office of Mental Retardation and Developmental Disabilities and by NIH grants HD38295 to Y.W.H. and HD43960 to Dr. Jerzy Wegiel.


  1. 1.
    Higdon JV, Frei B (2003) Tea catechins and polyphenols: health effects, metabolism, and antioxidant functions. Crit Rev Food Sci Nutr 43:89–143PubMedCrossRefGoogle Scholar
  2. 2.
    Yang CS, Maliakal P, Meng X (2002) Inhibition of carcinogenesis by tea. Annu Rev Pharmacol Toxicol 42:25–54PubMedCrossRefGoogle Scholar
  3. 3.
    Lin JK, Liang YC, Lin-Shiau SY (1999) Cancer chemoprevention by tea polyphenols through mitotic signal transduction blockade. Biochem Pharmacol 58:911–915PubMedCrossRefGoogle Scholar
  4. 4.
    Mandel S, Weinreb O, Amit T et al (2004) Cell signaling pathways in the neuroprotective actions of the green tea polyphenol (−)-epigallocatechin-3-gallate: implications for neurodegenerative diseases. J Neurochem 88:1555–1569PubMedCrossRefGoogle Scholar
  5. 5.
    Shirai N, Suzuki H (2004) Effect of dietary docosahexaenoic acid and catechins on maze behavior in mice. Ann Nutr Metab 48:51–58PubMedCrossRefGoogle Scholar
  6. 6.
    Unno K, Takabayashi F, Kishido T et al (2004) Suppressive effect of green tea catechins on morphologic and functional regression of the brain in aged mice with accelerated senescence (SAMP10). Exp Gerontol 39:1027–1034PubMedCrossRefGoogle Scholar
  7. 7.
    Haque AM, Hashimoto M, Katakura M et al (2006) Long-term administration of green tea catechins improves spatial cognition learning ability in rats. J Nutr 136:1043–1047PubMedGoogle Scholar
  8. 8.
    van Praag H, Lucero MJ, Yeo GW et al (2007) Plant-derived flavanol (−)epicatechin enhances angiogenesis and retention of spatial memory in mice. J Neurosci 27:5869–5878PubMedCrossRefGoogle Scholar
  9. 9.
    Reeves RH, Irving NG, Moran TH et al (1995) A mouse model for Down syndrome exhibits learning and behaviour deficits. Nat Genet 11:177–184PubMedCrossRefGoogle Scholar
  10. 10.
    Akeson EC, Lambert JP, Narayanswami S et al (2001) Ts65Dn – localization of the translocation breakpoint and trisomic gene content in a mouse model for Down syndrome. Cytogenet Cell Genet 93:270–276PubMedCrossRefGoogle Scholar
  11. 11.
    Reeves RH, Baxter LL, Richtsmeier JT (2001) Too much of a good thing: mechanisms of gene action in Down syndrome. Trends Genet 17:83–88PubMedCrossRefGoogle Scholar
  12. 12.
    Escorihuela RM, Fernandez-Teruel A, Vallina IF et al (1995) A behavioral assessment of Ts65Dn mice: a putative Down syndrome model. Neurosci Lett 199:143–146PubMedCrossRefGoogle Scholar
  13. 13.
    Demas GE, Nelson RJ, Krueger BK et al (1996) Spatial memory deficits in segmental trisomic Ts65Dn mice. Behav Brain Res 82:85–92PubMedCrossRefGoogle Scholar
  14. 14.
    Holtzman DM, Santucci D, Kilbridge J et al (1996) Developmental abnormalities and age-related neurodegeneration in a mouse model of Down syndrome. Proc Natl Acad Sci USA 93:13333–13338PubMedCrossRefGoogle Scholar
  15. 15.
    Fernandez F, Morishita W, Zuniga E et al (2007) Pharmacotherapy for cognitive impairment in a mouse model of Down syndrome. Nat Neurosci 10:411–413PubMedGoogle Scholar
  16. 16.
    Siarey RJ, Stoll J, Rapoport SI et al (1997) Altered long-term potentiation in the young and old Ts65Dn mouse, a model for Down Syndrome. Neuropharmacology 36:1549–1554PubMedCrossRefGoogle Scholar
  17. 17.
    Siarey RJ, Carlson EJ, Epstein CJ et al (1999) Increased synaptic depression in the Ts65Dn mouse, a model for mental retardation in Down syndrome. Neuropharmacology 38:1917–1920PubMedCrossRefGoogle Scholar
  18. 18.
    Kleschevnikov AM, Belichenko PV, Villar AJ et al (2004) Hippocampal long-term potentiation suppressed by increased inhibition in the Ts65Dn mouse, a genetic model of Down syndrome. J Neurosci 24:8153–8160PubMedCrossRefGoogle Scholar
  19. 19.
    Costa AC, Grybko MJ (2005) Deficits in hippocampal CA1 LTP induced by TBS but not HFS in the Ts65Dn mouse: a model of Down syndrome. Neurosci Lett 382:317–322PubMedCrossRefGoogle Scholar
  20. 20.
    Ramakrishna N, Meeker C, Li S et al (2005) Polymerase chain reaction method to identify Down syndrome model segmentally trisomic mice. Anal Biochem 340:213–219PubMedCrossRefGoogle Scholar
  21. 21.
    Anderson WW, Collingridge GL (2001) The LTP Program: a data acquisition program for on-line analysis of long-term potentiation and other synaptic events. J Neurosci Methods 108:71–83PubMedCrossRefGoogle Scholar
  22. 22.
    El-Sherif Y, Tesoriero J, Hogan MV et al (2003) Melatonin regulates neuronal plasticity in the hippocampus. J Neurosci Res 72:454–460PubMedCrossRefGoogle Scholar
  23. 23.
    Larson J, Wong D, Lynch G (1986) Patterned stimulation at the theta frequency is optimal for the induction of hippocampal long-term potentiation. Brain Res 368:347–350PubMedCrossRefGoogle Scholar
  24. 24.
    Bronner WE, Beecher GR (1998) Method for determining the content of catechins in tea infusions by high-performance liquid chromatography. J Chromatogr A 805:137–142PubMedCrossRefGoogle Scholar
  25. 25.
    Sang S, Lee MJ, Hou Z et al (2005) Stability of tea polyphenol (−)-epigallocatechin-3-gallate and formation of dimers and epimers under common experimental conditions. J Agric Food Chem 53:9478–9484PubMedCrossRefGoogle Scholar
  26. 26.
    Rock DM, Taylor CP (1986) Effects of diazepam, pentobarbital, phenytoin and pentylenetetrazol on hippocampal paired-pulse inhibition in vivo. Neurosci Lett 65:265–270PubMedCrossRefGoogle Scholar
  27. 27.
    Kapur J, Stringer JL, Lothman EW (1989) Evidence that repetitive seizures in the hippocampus cause a lasting reduction of GABAergic inhibition. J Neurophysiol 61:417–426PubMedGoogle Scholar
  28. 28.
    Malenka RC, Bear MF (2004) LTP and LTD: an embarrassment of riches. Neuron 44:5–21PubMedCrossRefGoogle Scholar
  29. 29.
    Siarey RJ, Kline-Burgess A, Cho M et al (2006) Altered signaling pathways underlying abnormal hippocampal synaptic plasticity in the Ts65Dn mouse model of Down syndrome. J Neurochem 98:1266–1277PubMedCrossRefGoogle Scholar
  30. 30.
    Maher P, Akaishi T, Abe K (2006) Flavonoid fisetin promotes ERK-dependent long-term potentiation and enhances memory. Proc Natl Acad Sci USA 103:16568–16573PubMedCrossRefGoogle Scholar
  31. 31.
    Kentrup H, Becker W, Heukelbach J et al (1996) Dyrk, a dual specificity protein kinase with unique structural features whose activity is dependent on tyrosine residues between subdomains VII and VIII. J Biol Chem 271:3488–3495PubMedCrossRefGoogle Scholar
  32. 32.
    Guimerá J, Casas C, Pucharcòs C et al (1996) A human homologue of Drosophila minibrain (MNB) is expressed in the neuronal regions affected in Down syndrome and maps to the critical region. Hum Mol Genet 5:1305–1310PubMedCrossRefGoogle Scholar
  33. 33.
    Shindoh N, Kudoh J, Maeda H et al (1996) Cloning of a human homolog of the Drosophila minibrain/rat DyrK gene from ‘the Down syndrome critical region” of chromosome 21. Biochem Biophys Res Commun 225:92–99PubMedCrossRefGoogle Scholar
  34. 34.
    Song WJ, Sternberg LR, Kasten-Sportès C et al (1996) Isolation of human and murine homologues of the Drosophila minibrain gene: human homologue maps to 21q22.2 in the Down syndrome “critical region”. Genomics 38:331–339PubMedCrossRefGoogle Scholar
  35. 35.
    Dowjat WK, Adayev T, Kuchna I et al (2007) Trisomy-driven overexpression of DYRK1A kinase in the brain of subjects with Down syndrome. Neurosci Lett 413:77–81PubMedCrossRefGoogle Scholar
  36. 36.
    Chen-Hwang MC, Chen HR, Elzinga M et al (2002) Dynamin is a minibrain kinase/dual specificity Yak1-related kinase 1A substrate. J Biol Chem 277:17597–17604PubMedCrossRefGoogle Scholar
  37. 37.
    Murakami N, Xie W, Lu RC et al (2006) Phosphorylation of amphiphysin 1 by Mnb/Dyrk1A, a kinase implicated in Down syndrome. J Biol Chem 281:23712–23724PubMedCrossRefGoogle Scholar
  38. 38.
    Adayev T, Chen-Hwang MC, Murakami N et al (2006) MNB/DYRK1A phosphorylation regulates the interactions of synaptojanin 1 with endocytic accessory proteins. Biochem Biophys Res Commun 351:1060–1065PubMedCrossRefGoogle Scholar
  39. 39.
    Bain J, McLauchlan H, Elliott M et al (2003) The specificities of protein kinase inhibitors: an update. Biochem J 371:199–204PubMedCrossRefGoogle Scholar
  40. 40.
    Adayev T, Chen-Hwang MC, Murakami N et al (2006) Kinetic property of a MNB/DYRK1A mutant suitable for the elucidation of biochemical pathways. Biochem 45:12011–12019CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Wen Xie
    • 1
    • 2
  • Narayan Ramakrishna
    • 4
  • Andrzej Wieraszko
    • 1
    • 2
    • 3
  • Yu-Wen Hwang
    • 1
    • 2
    • 4
  1. 1.CSI/IBR Center for Developmental Neuroscience, College of Staten IslandCity University of New YorkStaten IslandUSA
  2. 2.Doctoral Program in Biology, The Graduate CenterCity University of New YorkNew YorkUSA
  3. 3.Department of BiologyCollege of Staten IslandStaten IslandUSA
  4. 4.Molecular Biology DepartmentNew York State Institute for Basic Research in Developmental DisabilitiesStaten IslandUSA

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