Skip to main content
SpringerLink
Log in

Functional aspects of estrogen neuroprotection

  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

Evidence that estrogen protects neurons against toxic/ischemic insults or degenerative/aging processes is evident in a variety of in vitro and in vivo systems. However, a critical remaining question is: Does the demonstrated morphologic and neurochemical protection by estrogen lead to a preservation of brain function or an enhanced ability to recover? To date, little basic research is available on this issue. Cognition is a critical function that might provide a sensitive way to examine this question. As a first step, we present results showing that two chronic environmental insults, psychoactive drugs and stress, produce gender-specific responses in cognitive abilities. Specifically, females appear less sensitive than males to cognitive impairments following chronic exposure to these factors. Results are presented in male and female rats utilizing cognitive tests that assess visual (object recognition) and spatial memory (object placement and radial arm maze) following chronic amphetamine, methamphetamine, or daily restraint stress. Following regimes of chronic stress or amphetamine, males were impaired on these tasks while females were either unaffected, less affected, or enhanced in performance. These observations suggest that differences in circulating gonadal hormone levels between the sexes may contribute to the differential sensitivity of the sexes and provide endogenous neuroprotection for females. Surprisingly, ovariectomized females were still not impaired following a stress regimen that impaired males (21 d of daily restraint). These data taken together with neurochemical data on estrogen neuroprotective effects indicate that it is possible that neuroprotection by estrogen may result from hormone action both during sexual differentiation (organizational effect) and in adulthood (activational effect). These considerations and possible unwanted/untoward effects of chronic estrogen use are discussed in relation to the use of selective estrogen receptor modulators for chronic treatment of both males and females. In conclusion, although compelling evidence for neuroprotection by estrogen has been presented in anatomic and neurochemical studies, it is clear that the functional/behavioral aspects need further investigation.

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

Similar content being viewed by others

References

  1. Matsumoto, A. (1991). Psychoneuroendocrinology 16, 25–40.

    Article  PubMed  CAS  Google Scholar 

  2. Dohanich, G. (2002). In: Hormones, brain and behavior. Pfaff, D. W., Arnold, A. P., Etgen, A. M., Fahrbach, S. E., and Rubin, R. T. (eds.). Academic: New York.

    Google Scholar 

  3. Sherwin, B. B. (2002). Trends Pharmacol. Sci. 23(11), 527–534.

    Article  PubMed  CAS  Google Scholar 

  4. Henderson, V. W. (1997). Neurology 48(S7), S27-S35.

    PubMed  CAS  Google Scholar 

  5. Garcia-Segura, L. M., Azcoitia, I., and DonCarlos, L. L. (2001). Prog. Neurobiol. 63, 29–60.

    Article  PubMed  CAS  Google Scholar 

  6. Wise, P. M., Dubal, D. B., Wilson, M. E., Rau, S. W., Bottner, M., and Rosewell, K. L. (2001). Brain Res. Rev. 37(1–3), 313–319.

    Article  PubMed  CAS  Google Scholar 

  7. Lannert, H., Wirtz, P., Schuhmann, V., and Galmbacher, R. (1998). J. Neuroal Transm. 105, 1045–1063.

    Article  CAS  Google Scholar 

  8. Dluzen, D. E. and McDermott, J. L. (2002). Ann. NY Acad. Sci. 965, 136–156.

    Article  PubMed  CAS  Google Scholar 

  9. Sawada, H., Ibi, M., Kihara, T., et al. (2002). Neuropharmacology 42, 1056–1064.

    Article  PubMed  CAS  Google Scholar 

  10. Luine, V. N. (2002). Stress 5(3), 205–216.

    Article  PubMed  CAS  Google Scholar 

  11. McEwen, B. (2002). Recent Prog. Horm. Res. 57, 357–384.

    Article  PubMed  CAS  Google Scholar 

  12. Mizoguchi, K., Kunishita, T., Chui, D. H., and Tabra, T. (1992). Neurosci. Lett. 138, 157–160.

    Article  PubMed  CAS  Google Scholar 

  13. Robinson, T. E. and Kolb, B. (1997). J. Neurosci. 21, 8491–8497.

    Google Scholar 

  14. Camp, D. M. and Robinson, T. E. (1988). Behav. Brain. Res. 30(1), 69–88.

    Article  PubMed  CAS  Google Scholar 

  15. Becker, J. B. and Beer, M. E. (1986). Neurosci. Lett. 23, 203–208.

    Google Scholar 

  16. Alexander, G. E., Crutcher, M. D., and DeLong, M. R. (1990). Prog. Brain Res. 85, 119–146.

    Article  PubMed  CAS  Google Scholar 

  17. Nestler, E. G. (2001). Nature 2, 119–128.

    CAS  Google Scholar 

  18. Viaud, M. D. and White, N. M. (1989). Behav. Brain Res. 32, 31–42.

    Article  PubMed  CAS  Google Scholar 

  19. Packard, M. G., Cahill, L., and McGaugh, J. L. (1994). Proc. Natl. Acad. Sci. USA 91, 8477–8481.

    Article  PubMed  CAS  Google Scholar 

  20. Harper Mozley, L., Gur, R. C., David Mozley, P., and Gur, R. E. (2001). Am. J. Psychiatry 158, 1492–1499.

    Article  Google Scholar 

  21. Bisagno, V., Ferguson, D., and Luine, V. (2003). Pharmacol. Biochem. Behav. 74, 859–867.

    Article  PubMed  CAS  Google Scholar 

  22. Quinones-Jenab, V., Perrotti, L., Fabian, S., Chin, J., Russo, S., and Jenab, S. (2001). Ann. NY Acad. Sci. 937, 140–171.

    Article  PubMed  CAS  Google Scholar 

  23. Roth, M. E., Larson, E. B., and Carroll, M. E. (2002). Drug Alcohol Depend. 66, S2-S202.

    Article  Google Scholar 

  24. Ennaceur, A. and Delacour, J. (1988). Behav. Brain Res. 31, 47–59.

    Article  PubMed  CAS  Google Scholar 

  25. Beck, K. D. and Luine, V. N. (1999). Brain Res. 830, 56–71.

    Article  PubMed  CAS  Google Scholar 

  26. Miller, D. B., Ali, S. F., O’Callaghan, J. P., and Laws, S. C. (1998). Ann. NY Acad. Sci. 844, 153–165.

    Article  PubMed  CAS  Google Scholar 

  27. Bisagno, V., Ferguson, D., and Luine, V. (2002). Brain Res. 940, 95–101.

    Article  PubMed  CAS  Google Scholar 

  28. Mumby, D. G., Gaskin, S., Glenn, M. J., Schramek, T. E. and Lehmann, H. (2002). Learning Memory 9, 49–57.

    Article  PubMed  Google Scholar 

  29. Ennaceur, A., Neave, N., and Aggleton, J. P. (1997). Exp. Brain Res. 113, 509–519.

    Article  PubMed  CAS  Google Scholar 

  30. Cancela, L. M., Basso, A. M., Martijena, I. D., Capriles, N. R., and Molina, V. A. (2001). Brain Res. 309, 179–186.

    Article  Google Scholar 

  31. Wallace, T. L., Gudelsky, G. A., and Vorhees, C. V. (1999). J. Neurosci. 19, 9141–9148.

    PubMed  CAS  Google Scholar 

  32. Friedman, S. D., Castaneda, E., and Hodge, G. K. (1998). Pharmacol. Biochem. Behav. 61, 35–44.

    Article  PubMed  CAS  Google Scholar 

  33. Volkow, N. D., Chang, L., Wang, G. J., et al. (2001). Am. J. Psychiatry 158, 377–382.

    Article  PubMed  CAS  Google Scholar 

  34. Simon, S. L., Domier, C., Carnell, J., Brethen, P., Rawson, R., and Ling, W. (2000). Am. J. Addict. 3, 222–231.

    Article  Google Scholar 

  35. McKetin, R. and Mattick, R. P. (1997). Drug Alcohol Depend. 48, 235–242.

    Article  PubMed  CAS  Google Scholar 

  36. Ornstein, T. J., Iddon, J. L., Baldacchino, A. M., et al. (2000). Neurospychopharmacology 23, 113–116.

    Article  CAS  Google Scholar 

  37. Luine, V., Beck, K., Bowman, R. and Kneavel, M. (2001). In: Neuroplasticity, development and steroid hormone action. Handa, R. J., Hayaski, S., Terasawas, E., and Kawata, M. (eds.). CRC Press: Boca Raton, FL.

    Google Scholar 

  38. Bowman, R. E., Beck, K., and Luine, V. N. (2003). Horm. Behav. 43, 48–59.

    Article  PubMed  CAS  Google Scholar 

  39. Watanabe, Y., Gould, E., and McEwen, B. S. (1992). Brain Res. 588, 341–345.

    Article  PubMed  CAS  Google Scholar 

  40. Luine, V. and Rodriguez, M. (1994). Behav. Neural Biol. 62, 230–236.

    Article  PubMed  CAS  Google Scholar 

  41. Bowman, R. E., Zrull, M. C., and Luine, V. N. (2001). Brain Res. 904, 279–289.

    Article  PubMed  CAS  Google Scholar 

  42. Beck, K. D. and Luine, V. N. (1999). Brain Res. 830, 56–71.

    Article  PubMed  CAS  Google Scholar 

  43. Beck, K. D. and Luine, V. N. (2002). Physiol. Behav. 75, 661–673.

    Article  PubMed  CAS  Google Scholar 

  44. Luine, V., Martinez, C., Villegas, M., Magarinos, A. M., and McEwen, B. S. (1996). Physiol. Behav. 59, 27–32.

    Article  PubMed  CAS  Google Scholar 

  45. Luine, V., Villegas, M., Martinez, C., and McEwen, B. S. (1994). Brain Res. 639, 167–170.

    Article  PubMed  CAS  Google Scholar 

  46. Vongher, J. M. and Frye, C. A. (1999). Pharmacol. Biochem. Behav. 64(4), 777–785.

    Article  PubMed  CAS  Google Scholar 

  47. Hovartz, K. M., Hartig, W., Van Der Veen, R., et al. (2002). Neuroscience 110(3), 489–504.

    Article  Google Scholar 

  48. Jacobs, D. M., Tang, M. X., Stern, Y., et al. (1998). Neurology 50(2), 368–373.

    PubMed  CAS  Google Scholar 

  49. Cyr, M., Landry, M., and Di Paolo, T. (2000). Neuroendocrinology 23(1), 69–78.

    CAS  Google Scholar 

  50. Landry, M., Levesque, D., and Di Paolo, T. (2002). Neuroendocrinology 76(4), 214–222.

    Article  PubMed  CAS  Google Scholar 

  51. Cyr, M., Ghribi, O., Thibault, C., Morissette, M., Landry, M., and Di Paolo, T. (2001). Brain Res. Rev. 37, 153–161.

    Article  PubMed  CAS  Google Scholar 

  52. Callier, S., Morissette, M., Grandbois, M., Pelaprat, D., and Di Paolo, T. (2001). Synapse 41(2), 131–138.

    Article  PubMed  CAS  Google Scholar 

  53. Grandbois, M., Morissette, M., Callier, S., and Di Paolo, T. (2000). Neuroreport 7(11), 343–346.

    Article  Google Scholar 

  54. Lacreuse, A., Wilson, M. E., and Herndon, J. G. (2002). Neurobiol. Aging 23, 589–560.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Graduate Program in Psychology, Biopsychology Subprogram, CUNY Graduate School and University Center, New York, NY

    Rachel E. Bowman & Victoria N. Luine

  2. Department of Psychology, Sacred Heart University, Fairfield, CT

    Rachel E. Bowman

  3. Department of Psychology, Hunter College of CUNY, 695 Park Avenue, 10021, New York, NY

    Veronica Bisagno, Rachel E. Bowman & Victoria N. Luine

Authors
  1. Veronica Bisagno
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rachel E. Bowman
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Victoria N. Luine
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Victoria N. Luine.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bisagno, V., Bowman, R.E. & Luine, V.N. Functional aspects of estrogen neuroprotection. Endocr 21, 33–41 (2003). https://doi.org/10.1385/ENDO:21:1:33

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1385/ENDO:21:1:33

Key Words

Search

Navigation