Endocrine

, Volume 21, Issue 1, pp 33–41 | Cite as

Functional aspects of estrogen neuroprotection

  • Veronica Bisagno
  • Rachel E. Bowman
  • Victoria N. Luine
Article

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.

Key Words

Estradiol neuroprotection stress psychostimulants behavior cognition 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Matsumoto, A. (1991). Psychoneuroendocrinology 16, 25–40.PubMedCrossRefGoogle Scholar
  2. 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. 3.
    Sherwin, B. B. (2002). Trends Pharmacol. Sci. 23(11), 527–534.PubMedCrossRefGoogle Scholar
  4. 4.
    Henderson, V. W. (1997). Neurology 48(S7), S27-S35.PubMedGoogle Scholar
  5. 5.
    Garcia-Segura, L. M., Azcoitia, I., and DonCarlos, L. L. (2001). Prog. Neurobiol. 63, 29–60.PubMedCrossRefGoogle Scholar
  6. 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.PubMedCrossRefGoogle Scholar
  7. 7.
    Lannert, H., Wirtz, P., Schuhmann, V., and Galmbacher, R. (1998). J. Neuroal Transm. 105, 1045–1063.CrossRefGoogle Scholar
  8. 8.
    Dluzen, D. E. and McDermott, J. L. (2002). Ann. NY Acad. Sci. 965, 136–156.PubMedCrossRefGoogle Scholar
  9. 9.
    Sawada, H., Ibi, M., Kihara, T., et al. (2002). Neuropharmacology 42, 1056–1064.PubMedCrossRefGoogle Scholar
  10. 10.
    Luine, V. N. (2002). Stress 5(3), 205–216.PubMedCrossRefGoogle Scholar
  11. 11.
    McEwen, B. (2002). Recent Prog. Horm. Res. 57, 357–384.PubMedCrossRefGoogle Scholar
  12. 12.
    Mizoguchi, K., Kunishita, T., Chui, D. H., and Tabra, T. (1992). Neurosci. Lett. 138, 157–160.PubMedCrossRefGoogle Scholar
  13. 13.
    Robinson, T. E. and Kolb, B. (1997). J. Neurosci. 21, 8491–8497.Google Scholar
  14. 14.
    Camp, D. M. and Robinson, T. E. (1988). Behav. Brain. Res. 30(1), 69–88.PubMedCrossRefGoogle Scholar
  15. 15.
    Becker, J. B. and Beer, M. E. (1986). Neurosci. Lett. 23, 203–208.Google Scholar
  16. 16.
    Alexander, G. E., Crutcher, M. D., and DeLong, M. R. (1990). Prog. Brain Res. 85, 119–146.PubMedCrossRefGoogle Scholar
  17. 17.
    Nestler, E. G. (2001). Nature 2, 119–128.Google Scholar
  18. 18.
    Viaud, M. D. and White, N. M. (1989). Behav. Brain Res. 32, 31–42.PubMedCrossRefGoogle Scholar
  19. 19.
    Packard, M. G., Cahill, L., and McGaugh, J. L. (1994). Proc. Natl. Acad. Sci. USA 91, 8477–8481.PubMedCrossRefGoogle Scholar
  20. 20.
    Harper Mozley, L., Gur, R. C., David Mozley, P., and Gur, R. E. (2001). Am. J. Psychiatry 158, 1492–1499.CrossRefGoogle Scholar
  21. 21.
    Bisagno, V., Ferguson, D., and Luine, V. (2003). Pharmacol. Biochem. Behav. 74, 859–867.PubMedCrossRefGoogle Scholar
  22. 22.
    Quinones-Jenab, V., Perrotti, L., Fabian, S., Chin, J., Russo, S., and Jenab, S. (2001). Ann. NY Acad. Sci. 937, 140–171.PubMedCrossRefGoogle Scholar
  23. 23.
    Roth, M. E., Larson, E. B., and Carroll, M. E. (2002). Drug Alcohol Depend. 66, S2-S202.CrossRefGoogle Scholar
  24. 24.
    Ennaceur, A. and Delacour, J. (1988). Behav. Brain Res. 31, 47–59.PubMedCrossRefGoogle Scholar
  25. 25.
    Beck, K. D. and Luine, V. N. (1999). Brain Res. 830, 56–71.PubMedCrossRefGoogle Scholar
  26. 26.
    Miller, D. B., Ali, S. F., O’Callaghan, J. P., and Laws, S. C. (1998). Ann. NY Acad. Sci. 844, 153–165.PubMedCrossRefGoogle Scholar
  27. 27.
    Bisagno, V., Ferguson, D., and Luine, V. (2002). Brain Res. 940, 95–101.PubMedCrossRefGoogle Scholar
  28. 28.
    Mumby, D. G., Gaskin, S., Glenn, M. J., Schramek, T. E. and Lehmann, H. (2002). Learning Memory 9, 49–57.PubMedCrossRefGoogle Scholar
  29. 29.
    Ennaceur, A., Neave, N., and Aggleton, J. P. (1997). Exp. Brain Res. 113, 509–519.PubMedCrossRefGoogle Scholar
  30. 30.
    Cancela, L. M., Basso, A. M., Martijena, I. D., Capriles, N. R., and Molina, V. A. (2001). Brain Res. 309, 179–186.CrossRefGoogle Scholar
  31. 31.
    Wallace, T. L., Gudelsky, G. A., and Vorhees, C. V. (1999). J. Neurosci. 19, 9141–9148.PubMedGoogle Scholar
  32. 32.
    Friedman, S. D., Castaneda, E., and Hodge, G. K. (1998). Pharmacol. Biochem. Behav. 61, 35–44.PubMedCrossRefGoogle Scholar
  33. 33.
    Volkow, N. D., Chang, L., Wang, G. J., et al. (2001). Am. J. Psychiatry 158, 377–382.PubMedCrossRefGoogle Scholar
  34. 34.
    Simon, S. L., Domier, C., Carnell, J., Brethen, P., Rawson, R., and Ling, W. (2000). Am. J. Addict. 3, 222–231.CrossRefGoogle Scholar
  35. 35.
    McKetin, R. and Mattick, R. P. (1997). Drug Alcohol Depend. 48, 235–242.PubMedCrossRefGoogle Scholar
  36. 36.
    Ornstein, T. J., Iddon, J. L., Baldacchino, A. M., et al. (2000). Neurospychopharmacology 23, 113–116.CrossRefGoogle Scholar
  37. 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. 38.
    Bowman, R. E., Beck, K., and Luine, V. N. (2003). Horm. Behav. 43, 48–59.PubMedCrossRefGoogle Scholar
  39. 39.
    Watanabe, Y., Gould, E., and McEwen, B. S. (1992). Brain Res. 588, 341–345.PubMedCrossRefGoogle Scholar
  40. 40.
    Luine, V. and Rodriguez, M. (1994). Behav. Neural Biol. 62, 230–236.PubMedCrossRefGoogle Scholar
  41. 41.
    Bowman, R. E., Zrull, M. C., and Luine, V. N. (2001). Brain Res. 904, 279–289.PubMedCrossRefGoogle Scholar
  42. 42.
    Beck, K. D. and Luine, V. N. (1999). Brain Res. 830, 56–71.PubMedCrossRefGoogle Scholar
  43. 43.
    Beck, K. D. and Luine, V. N. (2002). Physiol. Behav. 75, 661–673.PubMedCrossRefGoogle Scholar
  44. 44.
    Luine, V., Martinez, C., Villegas, M., Magarinos, A. M., and McEwen, B. S. (1996). Physiol. Behav. 59, 27–32.PubMedCrossRefGoogle Scholar
  45. 45.
    Luine, V., Villegas, M., Martinez, C., and McEwen, B. S. (1994). Brain Res. 639, 167–170.PubMedCrossRefGoogle Scholar
  46. 46.
    Vongher, J. M. and Frye, C. A. (1999). Pharmacol. Biochem. Behav. 64(4), 777–785.PubMedCrossRefGoogle Scholar
  47. 47.
    Hovartz, K. M., Hartig, W., Van Der Veen, R., et al. (2002). Neuroscience 110(3), 489–504.CrossRefGoogle Scholar
  48. 48.
    Jacobs, D. M., Tang, M. X., Stern, Y., et al. (1998). Neurology 50(2), 368–373.PubMedGoogle Scholar
  49. 49.
    Cyr, M., Landry, M., and Di Paolo, T. (2000). Neuroendocrinology 23(1), 69–78.Google Scholar
  50. 50.
    Landry, M., Levesque, D., and Di Paolo, T. (2002). Neuroendocrinology 76(4), 214–222.PubMedCrossRefGoogle Scholar
  51. 51.
    Cyr, M., Ghribi, O., Thibault, C., Morissette, M., Landry, M., and Di Paolo, T. (2001). Brain Res. Rev. 37, 153–161.PubMedCrossRefGoogle Scholar
  52. 52.
    Callier, S., Morissette, M., Grandbois, M., Pelaprat, D., and Di Paolo, T. (2001). Synapse 41(2), 131–138.PubMedCrossRefGoogle Scholar
  53. 53.
    Grandbois, M., Morissette, M., Callier, S., and Di Paolo, T. (2000). Neuroreport 7(11), 343–346.CrossRefGoogle Scholar
  54. 54.
    Lacreuse, A., Wilson, M. E., and Herndon, J. G. (2002). Neurobiol. Aging 23, 589–560.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc 2003

Authors and Affiliations

  • Veronica Bisagno
    • 3
  • Rachel E. Bowman
    • 3
    • 1
    • 2
  • Victoria N. Luine
    • 3
    • 1
  1. 1.Graduate Program in Psychology, Biopsychology SubprogramCUNY Graduate School and University CenterNew York
  2. 2.Department of PsychologySacred Heart UniversityFairfield
  3. 3.Department of PsychologyHunter College of CUNYNew York

Personalised recommendations