Neurotoxicity Research

, Volume 3, Issue 3, pp 291–300 | Cite as

Tamoxifen eliminates estrogen’s neuroprotective effect upon MPTP-induced neurotoxicity of the nigrostriatal dopaminergic system

  • Dean E. Dluzen
  • Janet L. Mcdermott
  • Linda I. Anderson
Article

Abstract

The capacity for 17-a and 17-B estradiol to modulate MPTP-induced neurotoxicity of the nigrostriatal dopaminergic system and potential antagonism of this modulation by the anti-estrogen, tamoxifen, were evaluated. Treatment of retired breeder ovariect-omized C57/BI mice with17-B estradiol diminished the amount of striatal dopamine reduction resulting from MPTP treatment with striatal dopamine concentrations of these17-B estradiol treated mice failing to differ significantly from vehicle treated controls. A combined administration of17-B estradiol with tamoxifen abolished this neuroprotective effect of estrogen as striatal dopamine concentrations of this group were significantly lower than vehicle treated controls. Results to17-a estradiol were less effective since striatal dopamine concentrations of these mice following MPTP treatment were significantly decreased as compared with vehicle controls. In contrast to the nigrostriatal dopaminergic system, no statistically significant effects of these treatments were observed upon olfactory bulb dopamine concentrations. Taken together, these results show that17-B, but not an equivalent concentration of17-a, estradiol was effective in decreasing striatal dopamine neurotoxicity to MPTP. This effect of 17-Bestradiol was abolished by tamoxifen. These data have important implications regarding the mechanisms of estrogen-tamoxifen interactions within the nigrostriatal dopaminergic system as well as for clinical applications of tamoxifen within pre-menopausal women.

Keywords

Dopamine Striatum Olfactory Bulb Estradiol Parkinson’s Disease Neurodegeneration Cancer 

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References

  1. Ali, S. F. and Freyaldenhoven, T.E. (1999) MPTP — A model of Parkinson’s disease. In Bondy, S. C. (Ed): Chemicals and Neurodegenerative Disease (Scottsdale, AZ; Prominent Press), pp. 162–188.Google Scholar
  2. Behl, C. and Holsboer, F. (1999) The female sex hormone oestrogen as a neuroprotectant. TiPS20, 441–444.PubMedGoogle Scholar
  3. Behl, C, Skutella, T., Lezoualc’h, F., Post, A., Widmann, M., Newton, C. J. and Holsboer, F. (1997) Neuroprotection against oxidative stress by estrogens: Structure-activity relationship. Molec. Pharmacol.51, 535–541.Google Scholar
  4. Brooks, W. J., Jarvis, M. F. and Wagner, G. C. (1998) Influence of sex, age and strain of MPTF-induced neurotoxicity. Res. Comm. Subst. Abuse10, 181–184.Google Scholar
  5. Date, I., Felten. D. L. and Felten, S. Y. (1990) Long-term effect of MPTP in the mouse brain in relation to aging: neurochemical and immunocytochemical analysis. Brain Res.519, 266–276.PubMedCrossRefGoogle Scholar
  6. Dicko, A., Morissette, M., Ben Ameur, S.; Pezolet, M. and Di Paolo, T. (1999) Effect of estradiol and tamoxifen on brain membranes: Investigation by infrared and fluorescence spectroscopy. Brain Res. Bull.49, 401–405.PubMedCrossRefGoogle Scholar
  7. Dluzen, D. E. (1996) Effects of testosterone upon MPTP-induced neurotoxicity of the nigrostriatal dopaminergic system in male C57/BI mice. Brain Res.715, 113–118.PubMedCrossRefGoogle Scholar
  8. Dluzen, D. E. (1997) Estrogen decreases corpus striatal neurotoxicity in response to 6-hydroxydopamine. Brain Res.767, 340–344.PubMedCrossRefGoogle Scholar
  9. Dluzen, D. E. (2000) Neuroprotective effects of estrogen upon the nigrostriatal dopaminergic system. J. Neurocytol.29, 387–399.PubMedCrossRefGoogle Scholar
  10. Dluzen, D. E., Disshon, K. A. and McDermott, J. L. (1998) Estrogen as a modulator of striatal dopaminergic neurotoxicity. In Marwah, J. and Teitelbaum, H. (Eds) Recent Advances in Neurodegenerative Disorders (Scottsdale, AZ; Prominent Press), pp. 149–192.Google Scholar
  11. Dluzen, D. E. and McDermott, J. L. (2000a) Gender differences in the neurotoxicity of the nigrostriatal dopaminergic system: Implications for parkinson’s disease. J. Gender-Specific Med.3, 36–42.Google Scholar
  12. Dluzen, D. E. and McDermott, J. L. (2000b) Neuroprotective role of estrogen upon methamphetamine and related neurotoxins within the nigrostriatal dopaminergic system. Ann. NY Acad. Sci.914, 112–126.PubMedGoogle Scholar
  13. Dluzen, D. E., McDermott, J. L. and Liu, B. (1996a) Estrogen alters MPTP-induced neurotoxicity in female mice: Effects on striatal concentrations and release. J. Neuro-chem.66, 658–666.Google Scholar
  14. Dluzen, D. E., McDermott, J. L. and Liu, B. (1996b) Estrogen as a neuroprotectant against MPTP-induced neurotoxicity in C57/BI mice. Neurotox. Teratol.18, 603–606.CrossRefGoogle Scholar
  15. Farhat, M. Y., Abi-Younes, S., Dingaan, B., Vargas, R. and Ramwell, P. W. (1996) Estradiol increases cyclic adenosine monophosphate in rat pulmonary vascular smooth muscle cells by a nongenomic mechanism. J. Pharmacol. Exp. Ther.276, 652–657.PubMedGoogle Scholar
  16. Freyaldenhoven, T. E., Cadet, J. L. and Ali, S. F. (1996) The dopamine depleting effect of l-methyl-4-phe-nyl-l,2,3,6-tetrahydropyridine in CD-I mice are gender dependent. Brain Res.735, 232–238.PubMedCrossRefGoogle Scholar
  17. Gao, X. and Dluzen, D. E. (2000) Tamoxifen abolishes estrogen’s neuroprotective effect upon methamphetamine neurotoxicity of the nigrostriatal dopaminergic system. Neuroscience — submitted.Google Scholar
  18. Grandbois, M., Morissette, M., Callier, S. and Di Paolo, T. (2000) Ovarian steroids and raloxifene prevent MPTP-induced dopamine depletion in mice. NeuroRe-port11, 343–346.CrossRefGoogle Scholar
  19. Grandbois, M., Tanguay, B. and Di Paolo, T. (1999) Estradiol and dehydroepiandrosterone but not dihydrotestoster-one protect against MPTP-induced dopamine depletion in mice. Soc. Neurosci.25, 1595 (Abstract).Google Scholar
  20. Green, P. S., Bishop, J. and Simpkins, J. W. (1997) 17-estra-diol exerts neuroprotective effects on SK-N-SH cells. J. Neurosci.15, 511–515.Google Scholar
  21. Gupta, M., Gupta, B. K., Thomas, R., Bruemmer, V., Sladek Jr., J. R. and Felten, D. L. (1986) Aged mice are more sensitive to l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine treatment than young adults. Neurosci. Lett.70, 326–331.PubMedCrossRefGoogle Scholar
  22. Jordan, V. G. and Morrow, M. (1999) Tamoxifen, raloxifene and the prevention of breast cancer. Endocrin. Rev.20, 253–278.CrossRefGoogle Scholar
  23. McDermott, J. L., Anderson, L.I. and Dluzen, D. E. (1997) Interactive effects of tamoxifen and estrogen upon the nigrostriatal dopaminergic system. Neuroendocrinology66, 181–187.PubMedCrossRefGoogle Scholar
  24. McDermott, J. L., Anderson, L.I. and Dluzen, D. E. (1999) Interactive effects of tamoxifen and oestrogen upon the nigrostriatal dopaminergic system: Long-term treatments. J. Neuroendocrin.11, 801–803.CrossRefGoogle Scholar
  25. McDermott, J. L., Anderson, L.I. and Dluzen, D. E. (1998) Tamoxifen alters dopamine output through direct actions upon superfused corpus striatal tissue fragments. Neurochem Int.32, 299–307.PubMedCrossRefGoogle Scholar
  26. McEwen, B. S. and Alves, S. E. (1999) Estrogen actions in the central nervous system. Endocrin. Rev.20, 279–307.CrossRefGoogle Scholar
  27. Mermelstein, P. G., Becker, J. B. and Surmeier, D. J. (1996) Estradiol reduces calcium currents in rat neostriatal neurons via a membrane receptor. J. Neurosci.16, 595–604.PubMedGoogle Scholar
  28. Miller, D. B. (1998) Endocrine disruption: estrogen androgen and the nervous system. In Tilson, H. A. and Harry, G. J. (Eds.) Neurotoxicology (Taylor & Francis), pp. 201-217.Google Scholar
  29. Miller, D. B., Ali, S. F., O’Callaghan, J. P. and Laws, S. C. (1998) The impact of gender and estrogen on striatal dopaminergic neurotoxicity. Ann. NY Acad. Sci.844, 153–165.PubMedCrossRefGoogle Scholar
  30. Ramirez, V. D., Kim, K. and Dluzen, D. E. (1985) Progesterone action on the LHRH and the nigrostriatal dopamine neuronal systems:In vitro andin vivo studies. Rec. Prog. Horm. Res.41, 421–172.PubMedGoogle Scholar
  31. Simerly, R. B., Chang, C, Muramatsu, M. and Swanson, L. W. (1990) Distribution of androgen and estrogen receptor mRNA containing cells in the rat brain: Anin situ hybridization study. J. Comp. Neurol.294, 76–95.PubMedCrossRefGoogle Scholar
  32. Singer, C. A., Rogers, K. L., Strickland, T. M. and Dorsa, D. M. (1996) Estrogen protects primary cortical neurons from glutamate toxicity. Neurosci. Lett.212, 13–16.PubMedCrossRefGoogle Scholar
  33. Stephenson, J. (1999) Experts debate drugs for healthy women with breast cancer risk. J.A.M.A.282, 117–118.PubMedCrossRefGoogle Scholar
  34. Van Hartesveldt, C. and Joyce, J. N. (1986) Effects of estrogen on the basal ganglia. Neurosci. Biobehav. Rev.10, 1–14.PubMedCrossRefGoogle Scholar
  35. Wagner, G. C, Tekirian, T. L. and Cheo, C. T. (1993) Sexual differences in sensitivity to methamphetamine toxicity. J. Neural Transm.93, 67–70.CrossRefGoogle Scholar
  36. Yu, Y-L. and Liao, P-C. (2000) Sexual differences and estrous cycle in methamphetamine-induced dopamine and serotonin depletions in the striatum of mice. J. Neural Transm.107, 419–427.PubMedCrossRefGoogle Scholar
  37. Yu, Y-L. and Wagner, G. C. (1994) Influence of gonadal hormones on sexual differences in sensitivity to methamphetamine-induced neurotoxicity. J. Neural Transm. [P-D Sect]8, 215–221.CrossRefGoogle Scholar

Copyright information

© Springer 2001

Authors and Affiliations

  • Dean E. Dluzen
    • 1
  • Janet L. Mcdermott
    • 1
    • 2
  • Linda I. Anderson
    • 1
  1. 1.Department of Anatomy NortheasternOhio Universities College of MedicineJapan
  2. 2.Department of Internal MedicineEdwin Shaw HospitalJapan

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