Skip to main content

Facilitated Neurogenesis in the Developing Hippocampus After Intake of Theanine, an Amino Acid in Tea Leaves, and Object Recognition Memory

Abstract

Theanine, γ-glutamylethylamide, is one of the major amino acid components in green tea. In this study, cognitive function and the related mechanism were examined in theanine-administered young rats. Newborn rats were fed theanine through dams, which were fed water containing 0.3% theanine, and then fed water containing 0.3% theanine after weaning. Theanine level in the brain was under the detectable limit 6 weeks after the start of theanine administration. Theanine administration did not influence locomotor activity in the open-field test. However, rearing behavior was significantly increased in theanine-administered rats, suggesting that exploratory activity is increased by theanine intake. Furthermore, object recognition memory was enhanced in theanine-administered rats. The increase in exploratory activity in the open-field test seems to be associated with the enhanced object recognition memory after theanine administration. On the other hand, long-term potentiation (LTP) induction at the perforant path-granule cell synapse was not changed by theanine administration. To check hippocampal neurogenesis, BrdU was injected into rats 3 weeks after the start of theanine administration, and brain-derived neurotropic factor (BDNF) level was significantly increased at this time. Theanine intake significantly increased the number of BrdU-, Ki67-, and DCX-labeled cells in the granule cell layer 6 weeks after the start of theanine administration. This study indicates that 0.3% theanine administration facilitates neurogenesis in the developing hippocampus followed by enhanced recognition memory. Theanine intake may be of benefit to the postnatal development of hippocampal function.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

References

  1. Berninger B, Marty S, Zafra F, da Penha Berzaghi M, Thoenen H, Lindholm D (1995) GABAergic stimulation switches from enhancing to repressing BDNF expression in rat hippocampal neurons during maturation in vitro. Development 121:2327–2335

    PubMed  CAS  Google Scholar 

  2. Bolling BW, Chen CY, Blumberg JB (2009) Tea and health: preventive and therapeutic usefulness in the elderly? Curr Opin Clin Nutr Metab Care 12:42–48

    PubMed  Article  CAS  Google Scholar 

  3. Bryan J (2008) Psychological effects of dietary components of tea: caffeine and l-theanine. Nutr Rev 66:82–90

    PubMed  Article  Google Scholar 

  4. Cameron HA, Hazel TG, McKay RD (1998) Regulation of neurogenesis by growth factors and neurotransmitters. J Neurobiol 36:287–306

    PubMed  Article  CAS  Google Scholar 

  5. Cheng B, Mattson MP (1994) NT-3 and BDNF protect CNS neurons against metabolic/excitotoxic insults. Brain Res 640:56–67

    PubMed  Article  CAS  Google Scholar 

  6. Cho HS, Kim S, Lee SY, Park JA, Kim SJ, Chun HS (2008) Protective effect of the green tea component, l-theanine on environmental toxins-induced neuronal cell death. Neurotoxicology 29:656–662

    PubMed  Article  CAS  Google Scholar 

  7. Conner JM, Lauterborn JC, Yan Q, Gall CM, Varon S (1997) Distribution of brain-derived neurotrophic factor (BDNF) protein and mRNA in the normal adult rat CNS: evidence for anterograde axonal transport. J Neurosci 17:2295–2313

    PubMed  CAS  Google Scholar 

  8. Di X, Yan J, Zhao Y, Zhang J, Shi Z, Chang Y, Zhao B (2010) l-Theanine protects the APP (Swedish mutation) transgenic SH-SY5Y cell against glutamate-induced excitotoxicity via inhibition of the NMDA receptor pathway. Neuroscience 168:778–786

    PubMed  Article  CAS  Google Scholar 

  9. Egashira N, Hayakawa K, Mishima K, Kimura H, Iwasaki K, Fujiwara M (2004) Neuroprotective effect of gamma-glutamylethylamide (theanine) on cerebral infarction in mice. Neurosci Lett 363:58–61

    PubMed  Article  CAS  Google Scholar 

  10. Einöther SJ, Martens VE, Rycroft JA, De Bruin EA (2010) l-Theanine and caffeine improve task switching but not intersensory attention or subjective alertness. Appetite 54:406–409

    PubMed  Article  Google Scholar 

  11. Fukazawa Y, Saitoh Y, Ozawa F, Ohta Y, Mizuno K, Inokuchi K (2003) Hippocampal LTP is accompanied by enhanced F-actin content within the dendritic spine that is essential for late LTP maintenance in vivo. Neuron 38:447–460

    PubMed  Article  CAS  Google Scholar 

  12. Gage FH (2000) Mammalian neural stem cells. Science 287:1433–1438

    PubMed  Article  CAS  Google Scholar 

  13. Gomez-Ramirez M, Higgins BA, Rycroft JA, Owen GN, Mahoney J, Shpaner M, Foxe JJ (2007) The deployment of intersensory selective attention: a high-density electrical mapping study of the effects of theanine. Clin Neuropharmacol 30:25–38

    PubMed  Article  CAS  Google Scholar 

  14. Gonzalez de Mejia E, Ramirez-Mares MV, Puangpraphant S (2009) Bioactive components of tea: cancer, inflammation and behavior. Brain Behav Immune 23:721–732

    Article  CAS  Google Scholar 

  15. Graham HN (1992) Green tea composition, consumption, and polyphenol chemistry. Prev Med 21:334–350

    PubMed  Article  CAS  Google Scholar 

  16. Gundersen HJ, Bendtsen TF, Korbo L, Marcussen N, Moller A, Nielsen K, Nyengaard JR, Pakkenberg B, Sorensen FB, Vesterby A (1988) Some new, simple and efficient stereological methods and their use in pathological research and diagnosis. APMIS 96:379–394

    PubMed  Article  CAS  Google Scholar 

  17. Haskell CF, Kennedy DO, Milne AL, Wesnes KA, Scholey AB (2008) The effects of l-theanine, caffeine and their combination on cognition and mood. Biol Psychol 77:113–122

    PubMed  Article  Google Scholar 

  18. Hensch TK (2004) Critical period regulation. Annu Rev Neurosci 27:549–579

    PubMed  Article  CAS  Google Scholar 

  19. Ickes BR, Pham TM, Sanders LA, Albeck DS, Mohammed AH, Granholm AC (2000) Long-term environmental enrichment leads to regional increases in neurotrophin levels in rat brain. Exp Neurol 164:45–52

    PubMed  Article  CAS  Google Scholar 

  20. Ip NY, Li Y, Yancopoulos GD, Lindsay RM (1993) Cultured hippocampal neurons show responses to BDNF, NT-3, and NT-4, but not NGF. J Neurosci 13:3394–3405

    PubMed  CAS  Google Scholar 

  21. Kakuda T, Nozawa A, Sugimoto A, Niino H (2002) Inhibition by theanine of binding of [3H]AMPA, [3H]kainate, and [3H]MDL 105, 519 to glutamate receptors. Biosci Biotechnol Biochem 66:2683–2686

    PubMed  Article  CAS  Google Scholar 

  22. Kee N, Sivalingam S, Boonstra R, Wojtowicz JM (2002) The utility of Ki-67 and BrdU as proliferative markers of adult neurogenesis. J Neurosci Methods 115:97–105

    PubMed  Article  CAS  Google Scholar 

  23. Kelly SP, Gomez-Ramirez M, Montesi JL, Foxe JJ (2008) l-Theanine and caffeine in combination affect human cognition as evidenced by oscillatory alpha-band activity and attention task performance. J Nutr 138:1572S–1577S

    PubMed  CAS  Google Scholar 

  24. Kernie SG, Liebl DJ, Parada LF (2000) BDNF regulates eating behavior and locomotor activity in mice. EMBO J 19:1290–1300

    PubMed  Article  CAS  Google Scholar 

  25. Kobayashi T, Matsuno K, Murai M, Mita S (1997) Sigma 1 receptor subtype is involved in the facilitation of cortical dopaminergic transmission in the rat brain. Neurochem Res 22:1105–1109

    PubMed  Article  CAS  Google Scholar 

  26. Kobayashi K, Nagato Y, Aoi N, Juneja LR, Kim M, Yamamoto T, Sugimoto S (1998) Effects of l-theanine on the release of α-brain waves in human volunteers. Nippon Nogeikagaku Kaishi 72:153–157

    CAS  Google Scholar 

  27. Lee L, Duan W, Mattson MP (2002) Evidence that brain-derived neurotrophic factor is required for basal neurogenesis and mediates, in part, the enhancement of neurogenesis by dietary restriction in the hippocampus of adult mice. J Neurochem 82:1367–1375

    PubMed  Article  CAS  Google Scholar 

  28. Lindholm D, Carroll P, Tzimagiogis G, Thoenen H (1996) Autocrine-paracrine regulation of hippocampal neuron survival by IGF-1 and the neurotrophins BDNF, NT-3 and NT-4. Eur J Neurosci 8:1452–1460

    PubMed  Article  CAS  Google Scholar 

  29. Linnarsson S, Willson CA, Ernfors P (2000) Cell death in regenerating populations of neurons in BDNF mutant mice. Mol Brain Res 75:61–69

    PubMed  Article  CAS  Google Scholar 

  30. Marmigère F, Rage F, Tapia-Arancibia L (2003) GABA–glutamate interaction in the control of BDNF expression in hypothalamic neurons. Neurochem Int 42:353–358

    PubMed  Article  Google Scholar 

  31. McKay DL, Blumberg HR (2002) The role of tea in human health: an update. J Am Coll Nutr 21:1013

    Google Scholar 

  32. Nacher J, Crespo C, Mcewen BS (2001) Doublecortin expression in the adult rat telencephalon. Eur J Neurosci 14:629–644

    PubMed  Article  CAS  Google Scholar 

  33. Nakajo Y, Miyamoto S, Nakano Y, Xue JH, Hori T, Yanamoto H (2008) Genetic increase in brain-derived neurotrophic factor levels enhances learning and memory. Brain Res 1241:103–109

    PubMed  Article  CAS  Google Scholar 

  34. Numakawa T, Suzuki S, Kumamaru E, Adachi N, Richards M, Kunugi H (2010) BDNF function and intracellular signaling in neurons. Histol Histopathol 25:237–258

    PubMed  CAS  Google Scholar 

  35. Obrietan K, Gao XB, Van Den Pol AN (2002) Excitatory actions of GABA increase BDNF expression via a MAPK-CREB-dependent mechanism: a positive feedback circuit in developing neurons. J Neurophysiol 88:1005–1015

    PubMed  CAS  Google Scholar 

  36. Pietá Dias C, Martins de Lima MN, Presti-Torres J, Dornelles A, Garcia VA, Siciliani Scalco F, Rewsaat Guimarães M, Constantino L, Budni P, Dal-Pizzol F, Schröder N (2007) Memantine reduces oxidative damage and enhances long-term recognition memory in aged rats. Neuroscience 146:1719–1725

    PubMed  Article  Google Scholar 

  37. Shimbo M, Nakamura K, Shi HJ, Kizuki M, Seino K, Inose T, Takano T (2005) Green tea consumption in everyday life and mental health. Public Health Nutr 8:1300–1306

    PubMed  Article  Google Scholar 

  38. Suh SW, Fan Y, Hong SM, Liu Z, Matsumori Y, Weinstein PR, Swanson RA, Liu J (2005) Hypoglycemia induces transient neurogenesis and subsequent progenitor cell loss in the rat hippocampus. Diabetes 54:500–509

    PubMed  Article  CAS  Google Scholar 

  39. Terashima T, Takido J, Yokogoshi H (1999) Time-dependent changes of amino acids in the serum, liver, brain and urine of rats administered with theanine. Biosci Biotechnol Biochem 63:615–618

    PubMed  Article  CAS  Google Scholar 

  40. Unno T, Suzuki Y, Kakuda T, Hayakawa T, Tsuge H (1999) Metabolism of theanine, gamma-glutamylethylamide, in rats. J Agric Food Chem 47:1593–1596

    PubMed  Article  CAS  Google Scholar 

  41. Wu H, Friedman WJ, Dreyfus CF (2004) Differential regulation of neurotrophin expression in basal forebrain astrocytes by neuronal signals. J Neurosci Res 76:76–85

    PubMed  Article  CAS  Google Scholar 

  42. Yamada T, Terashima T, Wada K, Ueda S, Ito M, Okubo T, Juneja LR, Yokogoshi H (2007) Theanine, r-glutamylethylamide, increases neurotransmission concentrations and neurotrophin mRNA levels in the brain during lactation. Life Sci 81:1247–1255

    PubMed  Article  CAS  Google Scholar 

  43. Yamada T, Terashima T, Honma H, Nagata S, Okubo T, Juneja LR, Yokogoshi H (2008) Effects of theanine, a unique amino acid in tea leaves, on memory in a rat behavioral test. Biosci Biotechnol Biochem 72:1356–1359

    PubMed  Article  CAS  Google Scholar 

  44. Yamada T, Terashima T, Kawano S, Furuno R, Okubo T, Juneja LR, Yokogoshi H (2009) Theanine, gamma-glutamylethylamide, a unique amino acid in tea leaves, modulates neurotransmitter concentrations in the brain striatum interstitium in conscious rats. Amino Acids 36:21–27

    PubMed  Article  CAS  Google Scholar 

  45. Yokogoshi H, Terashima T (2000) Effect of theanine, r-glutamylethylamide, on brain monoamines, striatal dopamine release and some kinds of behavior in rats. Nutrition 16:776–777

    PubMed  Article  CAS  Google Scholar 

  46. Yokogoshi H, Kobayashi M, Mochizuki M, Terashima T (1998) Effect of theanine, r-glutamylethylamide, on brain monoamines and striatal dopamine release in conscious rats. Neurochem Res 23:667–673

    PubMed  Article  CAS  Google Scholar 

  47. Zambon AC, De Costa BR, Kanthasamy AG, Nguyen BQ, Matsumoto RR (1997) Subchronic administration of N-[2-(3, 4-dichlorophenyl) ethyl]-N-methyl-2-(dimethylamino) ethylamine (BD1047) alters sigma 1 receptor binding. Eur J Pharmacol 324:39–47

    PubMed  Article  CAS  Google Scholar 

  48. Zheng G, Sayama K, Okubo T, Juneja LR, Oguni I (2004) Anti-obesity effects of three major components of green tea, catechins, caffeine and theanine, in mice. In Vivo 18:55–62

    PubMed  CAS  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Atsushi Takeda.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Takeda, A., Sakamoto, K., Tamano, H. et al. Facilitated Neurogenesis in the Developing Hippocampus After Intake of Theanine, an Amino Acid in Tea Leaves, and Object Recognition Memory. Cell Mol Neurobiol 31, 1079–1088 (2011). https://doi.org/10.1007/s10571-011-9707-0

Download citation

Keywords

  • Theanine
  • Green tea
  • Neurogenesis
  • Memory
  • LTP
  • BDNF
  • Hippocampus