Skip to main content
Log in

Effects of genistein and daidzein on hippocampus neuronal cell proliferation and BDNF expression in H19-7 neural cell line

  • JNHA: Biology and Aging
  • Published:
The journal of nutrition, health & aging

Abstract

Objectives

Estrogen replacement therapy (ERT) reduces the risk of Alzheimer’s disease and symptoms in postmenopausal and elderly women. However, ERT is associated with increased risk of uterine and breast cancer. Dietary phytoestrogens have been suggested as a potential alternative to ERT, while little information is available regarding the effects and the underlying mechanisms of such treatment on central neuron function. The present study aimed to determine the effects of phytoestrogens including genistein and daidzein on the proliferation and survival of the hippocampus neural cells, which are of importance in learning and memory function.

Measurements

H19-7/IGF-IR neural cell line was cultured in DMEM absented of serum for 72 h, and treated with various concentrations of genistein, daidzein or 17β-estradiol. Neuronal cell viability and proliferation were determined by MTT and BrdU assay, respectively Cell cycle analysis was performed using flow cytometry. The effects of genistein and daidzein on brain-derived neurotrophic factor (BDNF) mRNA and protein expression were determined by RT-PCR and ELISA, respectively. The effect of Trk receptors inhibitor on genistein and daidzein — induced hippocampus neuronal cell proliferation was also examined.

Results

17β-estradiol, genistein and daidzein ranged from 20 nM to 2000 nM significantly promoted hippocampus neuronal cell viability and proliferation. Similar to the effect of 17β-estradiol, genistein and daidzein induced an increase in the percentage of cells in S phase. Genistein and daidzein significantly increased the expression of BDNF mRNA and protein levels. The effect of genistien and daidzein on hippocampus neuronal proliferation was blocked by K252a, a selective Trk receptors inhibitor.

Conclusion

This study concluded that genistein and daidzein improved hippocampus neuronal cell viability and proliferation in vitro. These neuroprotective effects might be mediated by BDNF-Trk pathway.

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

Access this article

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Yaffe K, Ettinger B, Pressman A, Seeley D, Whooley M, Schaefer C, Cummings S (1998) Neuropsychiatric function and dehydroepiandro sterone sulfate in elderly women: a prospective study. Biol Psychiatry 43:694–700.

    Article  PubMed  CAS  Google Scholar 

  2. Resnick SM, Metter EJ, Zonderman AB (1997) Estrogen replacement therapy and longitudinal decline in visual memory. A possible protective effect? Neurology 49:1491–1497.

    PubMed  CAS  Google Scholar 

  3. Shaywitz SE, Naftolin F, Zelterman D, Marchione KE, Holahan JM, Palter SF, Shaywitz BA (2003) Better oral reading and short-term memory in midlife, postmenopausal women taking estrogen. Menopause 10:420–426.

    Article  PubMed  Google Scholar 

  4. Hammond CB (1994) Women’s concerns with hormone replacement therapy-compliance issues. Fertil Steril 62:157S–160S.

    PubMed  CAS  Google Scholar 

  5. Messina M, Barnes S, Setchell KD (1997) Phyto-oestrogen s and breast cancer. Lancet 350:971–972.

    Article  PubMed  CAS  Google Scholar 

  6. Lephart ED, West TW, Weber KS, Rhees RW. Setehell KD, Adlercreutz H, Lund TD (2002) Neurobehavioral effects of dietary soy phytoestrogens. Neurotoxicol Teratol 24:5–16.

    Article  PubMed  CAS  Google Scholar 

  7. File SE, Jarrett N, Fluck E, Duffy R, Casey K, Wiseman H (2001) Eating soya improves human memory. Psychopharmacology (Berl) 257:430–436.

    Article  Google Scholar 

  8. Hartley DE, Forsling ML (2002) Renal response to arginine vasopressin during the oestrous cycle in the rat: comparison of glucose and saline infusion using physiological doses of vasopressin. Exp Physiol 87:9–15.

    Article  PubMed  CAS  Google Scholar 

  9. File SE, Heard JE, Rymer J (2002) Trough oestradiol levels associated with cognitive impairment in post-menopausal women after 10 years of oestradiol implants. Psychopharmacology (Berl) 161:107–112.

    Article  CAS  Google Scholar 

  10. Lu B, Figurov A (1997) Role of neurotrophins in synapse development and plasticity. Rev Neurosci 8:1–12.

    Article  PubMed  CAS  Google Scholar 

  11. Yamada T, McGeer PL, Baimbridge KG, McGeer EG (1990) Relative sparing in Parkinson’s disease of substantia nigra dopamine neurons containing calbindin-D28K. Brain Res 526:303–307.

    Article  PubMed  CAS  Google Scholar 

  12. Berchtold NC, Kesslak JP, Pike CJ, Adlard PA, Cotman CW (2001) Estrogen and exercise interact to regulate brain-derived neurotrophic factor mRNA and protein expression in the hippocampus. Eur J Neurosci 14:1992–2002.

    Article  PubMed  CAS  Google Scholar 

  13. Lee FS, Rajagopal R, Kim AH, Chang PC, Chao MV (2002) Activation of Trk neurotrophin receptor signaling by pituitary adenylate cyclase-activating polypeptides. J Biol Chem 277:9096–9102.

    Article  PubMed  CAS  Google Scholar 

  14. Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65:55–63.

    Article  PubMed  CAS  Google Scholar 

  15. Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254.

    Article  PubMed  CAS  Google Scholar 

  16. Perez-Martin M, Salazar V, Castillo C, Ariznavarreta C, Azcoitia I, Garcia-Segura LM, Tresguerres JA (2005) Estradiol and soy extract increase the production of new cell in the dentate gyrus of old rats. Exp Gerontol 40:450–453.

    Article  PubMed  CAS  Google Scholar 

  17. Brannvall K, Korhonen L, Lindholm D (2002) Estrogen-receptor-dependent regulation of neural stem cell proliferation and differentiation. Mol Cell Neurosci 21:512–520.

    Article  PubMed  CAS  Google Scholar 

  18. Ormerod BK, Galea LA (2001) Reproductive status influences cell proliferation and cell survival in the dentate gyrus of adult female meadow voles: a possible regulatory role for estradiol. Neuroscience 102:369–379.

    Article  PubMed  CAS  Google Scholar 

  19. Tanapat P, Hastings NB, Reeves AJ, Gould E (1999) Estrogen stimulates a transient increase in the number of new neurons in the dentate gyrus of the adult female rat. J Neurosci 19:5792–5801.

    PubMed  CAS  Google Scholar 

  20. Zhang L, Chang YH, Barker JL, Hu Q, Maric D, Li BS, Rubinow DR (2000) Testosterone and estrogen affect neuronal differentiation but not proliferation in early embryonic cortex of the rat: the possible roles of androgen and estrogen receptors. Neurosci Lett 281:57–60.

    Article  PubMed  CAS  Google Scholar 

  21. van Praag H, Schinder AF, Christie BR, Toni N, Palmer TD, Gage FH (2002) Functional neurogenesis in the adult hippocampus. Nature 415:1030–1034.

    Article  PubMed  Google Scholar 

  22. Pan Y, Anlhony M, Clarkson TB (1999) Effect of estradiol and soy phytoestrogens on choline acetyltransferase and nerve growth factor mRNAs in the frontal cortex and hippocampus of female rats. Proc Soc Exp Biol Med 221:118–125.

    Article  PubMed  CAS  Google Scholar 

  23. Murphy DD, Cole NB, Segal M (1998) Brain-derived neurotrophic factor mediates estradiol-induced dendritic spine formation in hippocampal neurons. Proc Natl Acad Sci USA 95:11412–11417.

    Article  PubMed  CAS  Google Scholar 

  24. Evangelopoulos ME, Weis J, Kruttgen A (2004) Neurotrophin effects on neuroblastoma cells: correlation with trk and p75NTR expression and influence of Trk receptor bodies. J Neurooncol 66:101–110.

    Article  PubMed  CAS  Google Scholar 

  25. Kovalchuk Y, Hanse E, Kafitz KW, Konnerth A (2002) Postsynaptic Induction of BDNF-Mediated Long-Term Potentiation. Science 295:1729–1734.

    Article  PubMed  CAS  Google Scholar 

  26. Barnabe-Heider F, Miller FD (2003) Endogenously produced neurotrophins regulate survival and differentiation of cortical progenitors via distinct signaling pathways. J Neurosci 23:5149–5160.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Meixia Pan, Hongyu Han, Caiyun Zhong or Qingshan Geng.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pan, M., Han, H., Zhong, C. et al. Effects of genistein and daidzein on hippocampus neuronal cell proliferation and BDNF expression in H19-7 neural cell line. J Nutr Health Aging 16, 389–394 (2012). https://doi.org/10.1007/s12603-011-0140-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12603-011-0140-3

Key words

Navigation