Journal of Neurocytology

, Volume 29, Issue 5–6, pp 387–399

Neuroprotective effects of estrogen upon the nigrostriatal dopaminergic system

  • Dean E. Dluzen


In this mini-review are first presented data which highlight the capacity and characteristics for estrogen to act as a neuroprotectant of the nigrostriatal dopaminergic system. Estrogen administration significantly attenuates the degree of striatal dopamine depletion to neurotoxins (MPTP, 6-OHDA and methamphetamine) which target the nigrostriatal dopaminergic system. This neuroprotection appears maximal with the 17-beta isomer, but some neuroprotection may also be present with the 17-alpha isomer of estradiol. Treatment with the anti-estrogen, tamoxifen, abolished estrogen's neuroprotective effects upon MPTP or methamphetamine-induced neurotoxicity. Estrogen also preserves striatal dopamine concentrations in gonadectomized male mice treated with MPTP, but neither testosterone nor dihydrotestosterone offer any neuroprotection. A brief review indicating a variety of potential means by which estrogen can function as a neuroprotectant is indicated. Included within this survey are presented estrogen's action as an antioxidant along with its capacity to affect monoamine oxidase, dopamine receptors/release, membrane morphology/fluidity, thermoregulation, blood flow and nitric oxide. This discussion is followed by a more detailed description of estrogen's actions upon the dopamine transporter, which is hypothesized to serve as one of the major mechanism involved with nigrostriatal dopaminergic neuroprotection. Overall, estrogen appears to inhibit dopamine transporter function by decreasing the affinity of the transporter. Such an effect could prevent neurotoxic agents from entering dopamine nerve terminals, thereby decreasing nigrostriatal neurodegeneration. Finally, some implications regarding this neuroprotectant capacity of estrogen are considered.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. ALI, S. F. & FREYALDENHOVEN, T. (1999) MPTP-a model of parkinson's disease. In Chemicals and Neurodegenerative Disease (edited by BONDY, S. C.) pp. 160–188. Scottsdale, AZ: Prominent Press.Google Scholar
  2. ANDERSON, L. I., MC DERMOTT, J. L. & DLUZEN, D. E. (1999) Estrogen-tamoxifen interactions upon striatal dopaminergic neurotoxicity produced by MPTP. Neuroscience Abstracts 25, 2088.Google Scholar
  3. ARNAULD, E., DUFY, B., PESTRE, M. & VINCENT, J. D. (1981) Effects of estrogens on the responses of caudate neurons to microiontophoretically applied dopamine. Neuroscience Letters 21, 325–331.PubMedGoogle Scholar
  4. ASTHANA, S., BAKER, L. D., CRAFT, S., RASKIND, M. A., AVERY, E., LOFGREEN, C. P., CHERRIER, M. & PLYMATE, S. R. (1999) Cognitive and neuroendocrine Estrogen and nigrostriatal neuroprotection 395 responses to estrogen in postmenopausal women with alzheimer's disease. Neuroscience Abstracts 25, 52.Google Scholar
  5. ATTALI, G., WEIZMAN, A., GIL-AD, I. & REHAVI, M. (1997) Opposite modulatory effects of ovarian hormones on rat brain dopamine and serotonin transporters. Brain Research 756, 153–159.PubMedGoogle Scholar
  6. AYRES, S., TANG, M. & SUBBIAH, M. T. (1996) Estradiol-17beta as an antioxidant: Some distinct features when compared with common fat-soluble antioxidants. Journal of Laboratory and Clinical Medicine 128, 367–375.PubMedGoogle Scholar
  7. BAKER, L. D., CRAFT, S., LOFGREEN, C., AVERY, E., RASKIND, M. A., CHERRIER, M., VEITH, R. C., PLYMATE, S. R. & ASTHANA, S. (1999) Dose-response estrogen-induced cognitive enhancements for postmenopausal women with Alzheimer's disease. Society for Neuroscience Abstracts 25, 53.Google Scholar
  8. BARBER, P. V., ARNOLD, A. G. & EVANS, G. (1976) Recurrent hormone dependent chorea: Effects of oestrogens and progesterones. Clinical Endocrinology 5, 291–293.PubMedGoogle Scholar
  9. BAZZETT, T. J. & BECKER, J. B. (1994) Sex differences in the rapid and acute effects of estrogen on striatal D2 dopamine receptor binding. Brain Research 637, 163–172.PubMedGoogle Scholar
  10. BECKER, J. B. (1990) Direct effect of 17 beta-estradiol on striatum: Sex differences in dopamine release. Synapse 5, 157–164.PubMedGoogle Scholar
  11. BECKER, J. B. (1999) Gender differences in dopaminergic function in striatum and nucleus accumbens. Pharmacology, Biochemistry and Behavior 64, 803–812.Google Scholar
  12. BECKER, J. B. & BEER, M. E. (1986) The influence of estrogen on nigrostriatal dopamine activity: Behavioral and neurochemical evidence for both pre-and post-synaptic components. Behavioral Brain Research 19, 27–33.Google Scholar
  13. BECKER, J. & RAMIREZ, V. D. (1981) Sex differences in the amphetamine stimulated release of catecholamines from rat striatal tissue in vitro. Brain Research 204, 361–372.PubMedGoogle Scholar
  14. BECKER, J. B. & RUDICK, C. N. (1999) Rapid effects of estrogen or progesterone on the amphetamine-induced increase in striatal dopamine are enhanced by estrogen priming: A microdialysis study. Pharmacology, Biochemistry and Behavior 64, 53–57.Google Scholar
  15. BEDARD, P. J., DI PAOLO, T., LANGELIER, P., POYET, P. & LABRIE, F. (1981) Behavioral and biochemical evidence of an effect of estradiol on striatal dopamine receptors. In Steroid Hormone Regulation of the Brain (edited by FUXE, K., GUSTAFSSON, J.-A. & WETTERBERG, L.) pp. 331–339. Oxford: Pergamon Press.Google Scholar
  16. BEDARD, P. J., LANGELIER, P. & VILLENEUVE, A. (1977) Oestrogens and extrapyramidal system. Lancet 2, 1367–1368.Google Scholar
  17. BEHL, C., SKUTELLA, T., LEZOUALC'H, F., POST, A., WIDMANN, M., NEWTON, C. J. & HOLSBOER, F. (1997) Neuroprotection against oxidative stress by estrogens: Structure-activity relationship. Molecular Pharmacology 51, 535–541.PubMedGoogle Scholar
  18. BEHL, C., WIDMANN, M., TRAPP, T. & HOLSBOER, F. (1995) 17-B estradiol protects neurons from oxidative stress-induced cell death in vitro. Biochemical and Biophysical Research Communications 216, 473–482.PubMedGoogle Scholar
  19. BROOKS, W. J., JARVIS, M. F. & WAGNER, G. C. (1989) Influence of sex, age and strain on MPTP-induced neurotoxicity. Research Communications on Substance Abuse 10, 181–184.Google Scholar
  20. CARDINALI, D. P. & GOMEZ, E. (1977) Changes in hypothalamic noradrenaline, dopamine and serotonin uptake after oestradiol administration to rats. Journal of Endocrinology 73, 181–182.PubMedGoogle Scholar
  21. CARDINALI, D. P., RITTA, M. N., VACAS, M. I., LOWENSTEIN, P. R., GEJMAN, P. V., GONZALEZ-SOLVEYRA, C. & PEREYRA, E. (1982) Molecular aspects of neuroendocrine integrative processes in the pineal gland. In The pineal gland and its endocrine role (edited by AXELROD, J., FRASCHINI, F. & VELO, G. P.) pp. 199–219. New York: Plenum Press.Google Scholar
  22. CASS, W. A., ZAHNISER, N. R., FLACH, K. A. & GERHARDT, G. A. (1993) Clearance of exogenous dopamine in rat dorsal striatum and nucleus accumbens: Role of metabolism and effects of locally applied uptake inhibitors. Journal of Neurochemistry 61, 2269–2278.PubMedGoogle Scholar
  23. CHIBA, K., TREVOR, A. J. & CASTAGNOLI, N. (1985) Active uptake of MPP+, a toxic metabolite of MPTP, by brain synaptosomes. Biochemistry and Biophysical Research Communications 128, 1228–1233.Google Scholar
  24. CHAKRAVORTY, S. G. & HALBREICH, U. (1997) The influence of estrogen on monoamine oxidase activity. Psychopharmacological Bulletin 33, 229–233.Google Scholar
  25. CHEN, J. C. & RAMIREZ, V. D. (1988) Comparison of the effect of prolactin on the dopamine release from the rat dorsal and ventral striatum and from the mediobasal hypothalamus in vitro. European Journal of Pharmacology 149, 1–8.PubMedGoogle Scholar
  26. CHEN, X. L., LI, R. & GUPTA, M. (1995) Estrogen may protect females from parkinson's disease. Society for Neuroscience Abstracts 21, 1252.Google Scholar
  27. CHEVILLARD, C., BARDEN, N. & SAAVEDRA, J. M. (1981) Estradiol treatment decreases typeA and increases type B monoamine oxidase in specific brain stem areas and cerebellum of ovariectomized rats. Brain Research 222, 177–181.PubMedGoogle Scholar
  28. CHIODO, L. A., CAGGIULA, A. R. & SALLER, C. F. (1981) Estrogen potentiates the stereotypy induced by dopamine agonists in the rat. Life Sciences 28, 827–835.PubMedGoogle Scholar
  29. CLARK, P. B. S. & REUBEN, M. (1995) Inhibition by dizocilpine (MK-801) of striatal dopamine release induced by MPTP and MPP+: Possible action at the dopamine transporter. British Journal of Pharmacology 114, 315–322.PubMedGoogle Scholar
  30. COSTA, M. M., REUS, V. I., WOLKOWITZ, O. M., MANFREDI, F. & LIEBERMAN, M. (1999) Estrogen replacement therapy and cognitive decline in memory impaired post-menopausal women. Biological Psychiatry 46, 182–188.PubMedGoogle Scholar
  31. CROWLEY, W. R., O'DONOHUE, T. L. & JACOBOWITZ, D. M. (1978) Sex differences in catecholamine content in discrete brain nuclei of the rat: Effects of neonatal castration or testosterone treatment. Acta Endocrinologica 89, 20–28.PubMedGoogle Scholar
  32. DEL ZOMPO, M., PICCARDI, M. P., RUIU, S., CORSINI, G. U. & VACCARI, A. (1992) Characterization of a putatively vesicular binding site for [3H]MPP+ in mouse striatal membranes. Brain Research 571, 354–357.PubMedGoogle Scholar
  33. DICKO, A., MORISSETTE, M., AMEUR, S. B., PEZOLET, M. & DI PAOLO, T. (1999) Effect of estradiol and tamoxifen on brain membranes: Investigation by infrared and fluorescence spectroscopy. Brain Research Bulletin 49, 401–405.PubMedGoogle Scholar
  34. DI PAOLO, T. (1994) Modulation of brain dopamine transmission by sex steroids. Reviews in Neuroscience 5, 27–42.Google Scholar
  35. DI PAOLO, T., DAIGLE, M. & LABRIE, F. (1984) Effect of estradiol and haloperidol on hypophysectomized rat brain dopamine receptors. Psychoneuroendocrinology 9, 399–404.PubMedGoogle Scholar
  36. DI PAOLO, T., POYET, P. & LABRIE, F. (1982) Effect of prolactin and estradiol on rat striatal dopamine receptors. Life Sciences 31, 2921–2929.PubMedGoogle Scholar
  37. DI PAOLO, T., ROULLIARD, C. & BEDARD, P. (1985) 17B-estradiol at a physiological dose acutely increases dopamine turnover in rat brain. European Journal of Pharmacology 117, 197–203.PubMedGoogle Scholar
  38. DISSHON, K. A., BOJA, J. W. & DLUZEN, D. E. (1998) Inhibition of striatal dopamine transporter activity by 17B-estradiol. European Journal of Pharmacology 345, 207–211.PubMedGoogle Scholar
  39. DISSHON, K. A. & DLUZEN, D. E. (1997) Estrogen as a modulator of MPTP-induced neurotoxicity: Effects upon corpus striatal dopamine release. Brain Research 764, 9–16.PubMedGoogle Scholar
  40. DISSHON, K. A. & DLUZEN, D. E. (1999a) Comparison of 17a-and 17B-estradiol upon striatal dopaminergic neurotoxicity produced by MPTP. Society for Neuroscience Abstracts 25, 2088.Google Scholar
  41. DISSHON, K. A. & DLUZEN, D. E. (1999b) Use of in vitro superfusion to assess the dynamics of striatal dopamine clearance: Influence of estrogen. Brain Research 842, 399–407.PubMedGoogle Scholar
  42. DISSHON, K. A. & DLUZEN, D. E. (2000) Estrogen reduces MPP+ acute striatal dopamine responses in vivo to the Neurotoxin in female, but not male rats. Brain Research 868, 95–104.PubMedGoogle Scholar
  43. DLUZEN, D. E. (1996) The effects of testosterone upon MPTP-induced neurotoxicity of the nigrostriatal dopaminergic system in male C57/Bl mice. Brain Research 715, 113–118.PubMedGoogle Scholar
  44. DLUZEN, D. E. (1997) Estrogen decreases corpus striatal neurotoxicity in response to 6-OHDA. Brain Research 767: 340–344.PubMedGoogle Scholar
  45. DLUZEN, D. E., DISSHON, K. A. & MC DERMOTT, J. L. (1998) Estrogen as a modulator of striatal dopaminergic neurotoxicity. In Recent Advances in Neurodegenerative Disorders (edited by MARWAH, J. & TIETELBAUM, H.) pp. 149–192. Scottsdale, AZ: Prominent Press.Google Scholar
  46. DLUZEN, D. E., LIU, B., CHEN, C.-Y. & DI CARLO, S. E. (1995) Daily spontaneous running alters behavioral and neurochemical indexes of nigrostriatal function. Journal of Applied Physiology 78, 1219–1224.PubMedGoogle Scholar
  47. DLUZEN, D. E. & MC DERMOTT, J. L. (2000) Neuroprotective role of estrogen upon methamphetamine and related neurotoxins within the nigrostriatal dopaminergic system. Annals of the New York Academy of Sciences 914, 112–126.PubMedGoogle Scholar
  48. DLUZEN, D. E., MC DERMOTT, J. L. & LIU, B. (1996a) Estrogen alters MPTP-induced neurotoxicity in female mice: Effects of striatal dopamine concentrations and release. Journal of Neurochemistry 66, 658–666.PubMedGoogle Scholar
  49. DLUZEN, D. E., MC DERMOTT, J. L. & LIU, B. (1996b) Estrogen as a neuroprotectant against MPTP-induced neurotoxicity in C57/Bl mice. Neurotoxicology and Teratology 18, 603–606.PubMedGoogle Scholar
  50. ENERSBY, C. A. & WILSON, C. A. (1974) The effect of ovarian steroids on the accumulation of 3H-labelled monoamines by hypothalamic tissue in vitro. Brain Research 73, 321–331.PubMedGoogle Scholar
  51. EUVRARD, C., OBERLANDER, C. & BOISSIER, J. R. (1980) Antidopaminergic effect of estrogen at the striatal level. Journal of Pharmacology and Experimental Therapeutics 214, 179–185.PubMedGoogle Scholar
  52. FALARDEAU, P. & DI PAOLO, T. (1987) Regional effect of estradiol on rat caudate putamen dopamine receptors: Lateral-medial differences. Neuroscience Letters 74, 43–48.PubMedGoogle Scholar
  53. FERNANDEZ-RUIZ, J. J., AMOR, J. C. & RAMOS, J. A. (1989) Time-dependent effects of estradiol and progesterone on the number of striatal dopaminergic D2-receptors. Brain Research 476, 388–395.PubMedGoogle Scholar
  54. FERNANDEZ-RUIZ, J. J., DE MIGUEL, R., HERNANDEZ, M. L., CEBEIRA, M. & RAMOS, J. A. (1992) Comparisons between brain dopaminergic neurons of juvenile and aged rats: Sex-related differences. Mechanisms of Ageing and Development 63, 45–55.PubMedGoogle Scholar
  55. FIGLEWICZ, D. P. (1999) Endocrine regulation of neurotransmitter transporters. Epilepsy Research 37, 203–210.PubMedGoogle Scholar
  56. FREYALDENHOVEN, T. E., CADET, J. L. & ALI, S. F. (1996) The dopamine depleting effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in CD-1 mice are gender dependent. Brain Research 735, 232–238.PubMedGoogle Scholar
  57. GAINETDINOV, R. R., FUMAGALLI, F., JONES, S. R. & CARON, M. G. (1997) Dopamine transporter is required for in vivo MPTP neurotoxicity: Evidence from mice lacking the transporter. Journal of Neurochemistry 69, 1322–1325.PubMedGoogle Scholar
  58. GAMBOA, E. T., ISAACS, G. & HARTER, D. H. Chorea associated with oral contraceptive therapy. Archives of Neurology 25, 112–114.Google Scholar
  59. GAO, X. & DLUZEN, D. E. (2000) Estrogen treatment protects, but does nor restore, nigrostriatal function in methamphetamine treated mice. The FASEB Journal 14, AI474.Google Scholar
  60. GIBBS, R. B. (1999) Treatment with estrogen and progesterone affects relative levels of brain derived neurotrophic factor mRNA and protein in different regions of the adult rat brain. Brain Research 844, 20–27.PubMedGoogle Scholar
  61. GLAZER, W. M., NAFTOLIN, F., MOORE, D. C., BOWERS, M. B. & MAC LUSKY, N. J. (1983) The relationship of circulating estradiol to tardive dykinesia in men and postmenopausal women. Psychoneuroendocrinology 8, 429–434.PubMedGoogle Scholar
  62. GOLDMAN, H., SKELLEY, E. B., SANDMAN, C. A., CASTIN, A. J. & MURPHY, S. (1976) Hormones and regional blood flow. Pharmacology, Biochemistry and Behavior 5 (Suppl 1), 165–169.Google Scholar
  63. GOODMAN, Y., BRUCE, A. J., CHENG, B. & MATTSON, M. P. (1996) Estrogens attenuate and corticosterone exacerbates excitotoxicity, oxidative injury and amyloid B-peptide toxicity in hippocampal neurons. Journal of Neurochemistry 66, 1836–1844.PubMedGoogle Scholar
  64. GORDON, J. H. & PERRY, K. O. (1983) Pre-and postsynaptic neurochemical alteration following estrogen-induced striatal dopamine hypo-and hypersensitivity. Brain Research Bulletin 10, 425–428.PubMedGoogle Scholar
  65. GRAHAM, D. G. (1984) Catecholamine toxicity: A proposal for the molecular pathogenesis of manganese neurotoxicity and Parkinson's disease. Neurotoxicity 5, 83–95.Google Scholar
  66. GRANDBOIS, M., TANGUAY, B. & DI PAOLO, T. (1999) Estradiol and dehydroepiandrosterone but not dihydrotestosterone protect against MPTP-induced dopamine depletion in mice. Society for Neuroscience Abstracts 25, 1595.Google Scholar
  67. GREEN, P. S., BISHOP, J. & SIMPKINS, J. W. (1997) 17a-estradiol exerts neuroprotective effects on SK-N-SH cells. Journal of Neuroscience 17, 511–515.PubMedGoogle Scholar
  68. GREEN, P. S., GRIDLEY, K. E. & SIMPKINS, J. W. (1996) Estradiol protects against B-amyloid (25–35)-induced toxicity in SK-N-SH human neuroblastoma cells. Neuroscience Letters 218, 165–168.PubMedGoogle Scholar
  69. HASHIMOTO, M., HOSSAIN, S. & MASUMURA, S. (1999) Effect of aging on plasma membrane fluidity of rat aortic endothelial cells. Experimental Gerontology 34, 687–698.PubMedGoogle Scholar
  70. HEIKKILA, R. E., YOUNGSTER, S. K., MANZINO, L., CABBAT, F. S. & DUVOISIN, R. C. (1985). Effects of 1-methyl-4-phenyl-1,2,5,6-tetrahydropryridine and related compounds on the uptake of [3H]3,4dihydroxyphenylethylamine and [3H]5-hydroxytryptamine on neostriatal synaptosomal preparations. Journal of Neurochemistry 44, 310–313.PubMedGoogle Scholar
  71. HRUSKA, R. E., LUDMER, L. M. & SILBERGELD, E. K. (1980) Characterization of the striatal dopamine receptor supersensitivity produced by estrogen treatment of male rats. Neuropharmacology 19, 923–926.PubMedGoogle Scholar
  72. HUANG, A., SUN, D., KALEY, G. & KOLLER, A. (1997) Estrogen maintains nitric oxide synthesis in arterioles of female hypertensive rats. Hypertension 29, 1351–1356.PubMedGoogle Scholar
  73. ISLES, C. G., HOLE, D. J., HAWTHORNE, V. M. & LEVER, A. F. (1992) Relation between coronary risk and coronary mortality in women of the Renfew and Paisley survey: Comparison with men. Lancet 339, 702–706.PubMedGoogle Scholar
  74. JABER, M., JONES, S., GIROS, B. & CARON, M. G. (1997) The dopamine transporter: A crucial component regulating dopamine transmission. Movement Disorders 12, 629–633.PubMedGoogle Scholar
  75. JAVITCH, J. A., D'AMATO, R. J., STRITTMATTER, S. M. & SYNDER, S. H. (1985) Parkinsonism-inducing neurotoxin, N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine: Uptake of the metabolite N-methyl-4-phenylpyridine by dopamine neurons explains selective neurotoxicity. Proceedings of the National Academy of Sciences of the USA 82, 2173–2177.PubMedGoogle Scholar
  76. JIN, B. K., SHIN, D. Y., JEONG, MI, Y., GWAG MI, R., BAIK, H. W., YOON, K. S., CHO, Y. H., JOO, W. S., KIM, Y. S. & BAIK, H. H. (1998) Melatonin protects nigral dopaminergic neurons from 1-methyl-4-phenylpyridinium (MPP+) neurotoxicity in rats. Neuroscience Letters 245, 61–64.PubMedGoogle Scholar
  77. JONES, S. R., GAINETDINOV, R. R., JABER, M. M., GIROS, B., WIGHTMAN, R. M. & CARON, M. G. (1998) Profound neuronal plasticity in response to inactivation of the dopamine transporter. Proceedings of the National Academy of Sciences of the USA 95, 4029–4034.PubMedGoogle Scholar
  78. JORDAN, V. G. & MORROW, M. (1999) Tamoxifen, raloxifene, and the prevention of breast cancer. Endocrine Reviews 20, 253–278.PubMedGoogle Scholar
  79. KLETZKY, O. A. & BORENSTEIN, R. (1987) Vasomotor instability of the menopause. In Menopause physiology and pharmacology (edited by MISHELL JR., D. R.) pp 53–65, Chicago: Year Book Medical Publishers Inc.Google Scholar
  80. KOLLER, W. C., BARR, A. & BIARY, N. (1982) Estrogen treatment of dyskinetic disorders. Neurology 32, 547–549.PubMedGoogle Scholar
  81. LAMMERS, C.-H., D'SOUZA, U., QIN, Z.-H., LEE, S.-H., YAJIMA, S. & MOURADIAN, M. M. (1999) Regulation of striatal dopamine receptors by estrogen. Synapse 34, 222–227.PubMedGoogle Scholar
  82. LEE, S.-H. & MOURADIAN, M. M. (1999) Up-regulation of D1A dopamine receptor gene transcription by estrogen. Molecular and Cellular Endocrinology 156, 151–157.PubMedGoogle Scholar
  83. LEIPHEIMER, R. E., ARVIN, M. A., FEDORKOVA, L., DISSHON, K. A. & DLUZEN, D. E. (1998) Estrogen modulation of MPP+-stimulated dopamine secretion in the corpus striatum of rats using in vivo and in vitro techniques. Society for Neuroscience Abstracts 24, 1723.Google Scholar
  84. LEVESQUE, D. & DI PAOLO, T. (1988) Rapid conversion of high into low striatal D2-dopamine receptor agonist binding sites after an acute physiological dose of 17B-estradiol. Neuroscience Letters 88, 113–118.PubMedGoogle Scholar
  85. LEVESQUE, D. & DI PAOLO, T. (1989) Chronic estradiol treatment increases ovariectomized rat striatal D-1 dopamine receptors. Life Sciences 45, 1813–1820.PubMedGoogle Scholar
  86. MAGYAR, K., SZENDE, B., LENGYEL, J., TARCZALI, J. & SZATMARY, I. (1998) The neuroprotective and neurorescue effects of (?)-deprenyl. Journal of Neural Transmission Suppl 52, 109–123.Google Scholar
  87. MARDER, K., TANG, M.-X., ALFARO, B., MEJIA, H., COTE, L., JACOBS, D., STERN, Y., SANO, M. & MAYEUX, M. (1998) Postmenopausal estrogen use and Parkinson's disease with and without dementia. Neurology 50, 1141–1143.PubMedGoogle Scholar
  88. MARSHALL, J. F., O'DELL, S. J. & WEIHMULLER, F. B. (1993) Dopamine-glutamate interactions in methamphetamine-induced neurotoxicity. Journal of Neural Transmission 91, 241–254.PubMedGoogle Scholar
  89. MC DERMOTT, J. L., KREUTZBERG, J. D., LIU, B. & DLUZEN, D. E. (1994a) Effects of estrogen treatment on sensorimotor task performance and brain dopamine concentrations in gonadectomized male and female CD-1 mice. Hormones and Behavior 28, 16–28.PubMedGoogle Scholar
  90. MC DERMOTT, J. L., LIU, B. & DLUZEN, D. E. (1994b) Sex differences and effects of estrogen on dopamine and DOPAC release from the striatum of male and female CD-1 mice. Experimental Neurology 125, 306–311.PubMedGoogle Scholar
  91. MC MILLAN, P. J., SINGER, C. A. & DORSA, D. M. (1996) The effect of ovariectomy and estrogen replacement on trkA and choline acetyltransferase mRNA expression in the basal forebrain of the adult female sprague dawley rat. Journal of Neuroscience 16, 1860–1865.PubMedGoogle Scholar
  92. MICHEL, P. P. & HEFTI, F. (1990) Toxicity of 6-hydroxydopamine and dopamine for dopaminergic neurons in culture. Journal of Neuroscience Research 26, 428–435.PubMedGoogle Scholar
  93. MICHEL, M. C., ROTHER, A., HIEMKE, C. & GHRAF, R. (1987) Inhibition of synaptosomal high-affinity uptake of dopamine and serotonin by estrogen agonists and antagonists. Biochemical Pharmacology 36, 3175–3180.PubMedGoogle Scholar
  94. MILLER, D. B. (1998) Endocrine disruption: Estrogen, androgen, and the nervous system. In Neurotoxicity (edited by TILSON, H. A. & HARRY, G. J.) pp. 201–218, Taylor & Francis.Google Scholar
  95. MILLER, D. B., ALI, S. F., O'CALLAGHAN, J. P. & LAWS, S. C. (1998) The impact of gender and estrogen on striatal dopamine neurotoxicity. Annals of the New York Academy of Sciences 844, 153–165.PubMedGoogle Scholar
  96. MIRANDA, R. C. & SOHRABJI, F. (1996) Gonadal steroid receptors: Possible roles in the etiology and therapy of cognitive and neurological disorders. Annals of Reproductive Medicine and Chemistry 31, 11–20.Google Scholar
  97. MIURA, T., MURAOKA, S. & OGISO, T. (1996) Inhibition of lipid peroxidation by estradiol and 2-hydroxyestradiol. Steroids 61, 379–383.PubMedGoogle Scholar
  98. MOOK-JUNG, I., JOO, I., SOHN, S., KWON, H. J., HUH, K. & JUNG, M. W. (1997) Estrogen blocks neurotoxic effects of B-amyloid (1–42) and induces neurite extension on B103 cells. Neuroscience Letters 235, 101–104.PubMedGoogle Scholar
  99. MOORADIAN, A. D. (1993) Antioxidant properties of steroids. Journal of Steroid Biochemistry 45, 509–511.Google Scholar
  100. MORISSETTE, M., BIRON, D. & DI PAOLO, T. (1990) Effect of estradiol and progesterone on rat striatal uptake sites. Brain Research Bulletin 25, 419–422.PubMedGoogle Scholar
  101. MORISSETTE, M., GARCIA-SEGURA, L.-M., BELANGER, A. & DI PAOLO, T. (1992) Changes of rat striatal neuronal membrane morphology and steroid content during the estrous cycle. Neuroscience 49, 893–902.PubMedGoogle Scholar
  102. MOY, L. Y., ALBERS, D. S. & SONSALLA, P. K. (1998) Lowering ambient or core body temperature elevates striatal MPP+ levels and enhances toxicity to dopamine neurons in MPTP-treated mice. Brain Research 790, 264–269.PubMedGoogle Scholar
  103. NABULSI, A. A., FOLSON, A. R., WHITE, A., PATSCH, W., HEISS, G., WU, K. K. & SZKLO, M. (1993) Association of hormone-replacement therapy with various cardiovascular risk factors in postmenopausal women. New England Journal of Medicine 328, 1069–1075.PubMedGoogle Scholar
  104. NAKANO, M., SUGIOKA, K., NAITO, I., TAKEKOSHI, S. & NIKI, E. (1987) Novel and potent biological antioxidants on membrane phospholipid peroxidation: 2-hydroxy estrone and 2-hydroxy estradiol. Biochemical and Biophysical Research Communications 142, 919–924.PubMedGoogle Scholar
  105. O'DELL, S. J., WEIHMULLER, F. B. & MARSHALL, J. (1991) Multiple methamphetamine injections induce marked increases in extracellular striatal dopamine which correlate with subsequent neurotoxicity. Brain Research 564, 256–260.PubMedGoogle Scholar
  106. OHKURA, T., TESHIMA, Y., ISSE, K., MATSUDA, H., INOUE, T., SAKAI, Y., IWASKI, N. & YAOI, Y. (1995) Estrogen increases cerebral and cerebellar blood flows in postmenopausal women. Menopause 2, 13–18.Google Scholar
  107. PASQUALINI, C., OLIVIER, V., GUIBERT, B., FRAIN, O. & LEVIEL, V. (1995) Acute stimulatory effect of estradiol on striatal dopamine synthesis. Journal of Neurochemistry 65, 1651–1657.PubMedGoogle Scholar
  108. RIEDERER, P., KONRADI, C., SCHAY, V., KIENZL, E., BIRKMAYER, G., DANIELCZYK, W., SOFIL, E. & YOUDIM, M. B. H. (1986) Localization of MAO-A and MAO-B in human brain: A step in understanding the therapeutic actions of L-deprenyl. Advances in Neurology 45, 111–118.Google Scholar
  109. RUIZ-LARREA, M. B., LEAL, A. M., LIZA, M., LACORT, M. & DE GROOT, H. (1994) Antioxidant effects of estradiol and 2-hydroxyestradiol on iron-induced lipid peroxidation of rat liver microsomes. Steroids 59, 383–388.PubMedGoogle Scholar
  110. RICAURTE, G. A., LANGSTON, J. W., DELANEY, L. E., IRWIN, I. & BROOKS, J. D. (1985) Dopamine uptake blockers protect against dopamine depleting effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the mouse striatum. Neuroscience Letters 59, 259–264.PubMedGoogle Scholar
  111. SANGHERA, M., MANAYE, K., MC MAHON, A., SONSALLA, P. K. & GERMAN, D. SC. (1997) Dopamine transporter mRNA levels are high in midbrain neurons vulnerable to MPTP. NeuroReport 8, 3327–3331.PubMedGoogle Scholar
  112. SANTIAGO, M., MACHARO, A. & CANO, J. (1994) Effect of L-arginine/nitric oxide pathway on MPP+-induced cell injury in the striatum of rats. British Journal of Pharmacology 111, 837–842.PubMedGoogle Scholar
  113. SATOH, N., YONEZAWA, A., TADANO, T., KISARA, K., ARAI, Y. & KINEMUCHI, H. (1987) Acute effects of a parkinsonism-inducing neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on mouse body temperature. Life Sciences 41, 1415–1424.PubMedGoogle Scholar
  114. SAUNDERS-PULLMAN, R., GORDON-ELLIOT, J., PARIDES, M., FAHN, S., SAUNDERS, H. R. & BRESSMAN, S. (1999) The effect of estrogen replacement on early parkinson's disease. Neurology 52, 1417–1421.PubMedGoogle Scholar
  115. SAUTTER, J., MEYER, M., SPENCER, C., SEILER, R. W. & WIDMER, H. R. (1998) Effects of combined BDNF and GDNF treatment on cultured dopaminergic midbrain neurons. NeuroReport 9, 1093–1096.PubMedGoogle Scholar
  116. SCHWARTING, R. K. W. & HUSTON, J. P. (1996) Unilateral 6-hydroxydopamine lesions of meso-striatal dopamine neurons and their physiological sequelae. Progress in Neurobiology 49, 215–266.PubMedGoogle Scholar
  117. SINGER, C. A., PANG, P. A., DOBIE, D. J. & DORSA, D. M. (1996a) Estrogen increases GAP-43 (Neuromodulin) mRNAin preoptic area of aged rats. Neurobiology of Aging 17, 661–663.PubMedGoogle Scholar
  118. SINGER, C. A., ROGERS, K. L., STRICKLAND, T. M. & DORSA, D. M. (1996b) Estrogen protects primary cortical neurons from glutamate toxicity. Neuroscience Letters 212, 13–16.PubMedGoogle Scholar
  119. SINGH, M., MEYER, E. M. & SIMPKINS, J. W. (1995) The effect of ovariectomy and estradiol replacement on brain-derived neurotrophic factor messenger ribonucleic acid expression in cortical and hippocampal brain regions of female sprague dawley rats. Endocrinology 136, 2320–2324.PubMedGoogle Scholar
  120. SPINA, M. B. & COHEN, G. (1989) Dopamine turnover and glutathione oxidation: Implications for parkinson's disease. Proceedings of the National Academy of Sciences of the USA 86, 1714–1718.Google Scholar
  121. STEPHENSON, J. (1999) Experts debate drugs for healthy women with breast cancer risk. Journal of the American Medical Association 282, 117–118.PubMedGoogle Scholar
  122. THOMPSON, T. L. (1999) Attenuation of dopamine uptake in vivo following priming with estradiol benzoate. Brain Research 834, 164–167.PubMedGoogle Scholar
  123. THOMPSON, T. L. & MOSS, R. L. (1994) Estrogen regulation of dopamine release in the nucleus accumbens: Estrogen and nigrostriatal neuroprotection 399 Genomic-and nongenomic-mediated effects. Journal of Neurochemistry 62, 1750–1756.PubMedGoogle Scholar
  124. TRANQUILLI, A. L., MAZZANTI, L., CUGINI, A. M., CESTER, N., GARZETTI, G. G. & ROMANINI, C. (1995) Transdermal estradiol and medroxyprogesterone acetate in hormone replacement therapy are both antioxidants. Gynecological Endocrinology 9, 137–141.PubMedGoogle Scholar
  125. TSAI, M. J. & LEE, E. H. Y. (1998) Nitric oxide donors protect cultured rat astrocytes from 1-methyl-4-phenylpyridinium-induce toxicity. Free Radical Biology and Medicine 24, 705–713.PubMedGoogle Scholar
  126. VACCARI, A. & BIASSONI, R. (1982) Gonadal influence on the inhibition of monoamine oxidase type B activity. Journal of Neuroscience Research 8, 13–19.PubMedGoogle Scholar
  127. VACCARI, A., DEL ZOMPO, M., MELIS, F., GESSA, G. L. & ROSSETTI, Z. L. (1991) Interactions of 1-methyl-4-phenylpyridinium ion and tyramine with a site putatively involved in the striatal vesicular release of dopamine. British Journal of Pharmacology 104, 573–574.PubMedGoogle Scholar
  128. VAN HARTESVELDT, C. & JOYCE, J. N. (1986) Effects of estrogen on the basal ganglia. Neuroscience & Biobehavioral Reviews 10, 1–14.Google Scholar
  129. VAN HORNE, C., HOFFER, B. J., STROMBERT, I. & GERHARDT, G. A. (1992) Clearance and diffusion of locally applied dopamine in normal and 6-hydroxydopamine-lesioned rat striatum. Journal of Pharmacology and Experimental Therapeutics 263, 1285–1292.PubMedGoogle Scholar
  130. WAGNER, G. C., TEKIRIAN, T. L. & CHEO, C. T. (1993) Sexual differences in sensitivity to methamphetamine toxicity. Journal of Neural Transmission 93, 67–70.PubMedGoogle Scholar
  131. WEAVER, JR. C. E., PARK-CHUNG, M., GIBBS, T. T. & FARB, D. H. (1997) 17B-estradiol protects against NMDA-induced excitotoxicity by direct inhibition of NMDA receptors. Brain Research 761, 338–341.PubMedGoogle Scholar
  132. WEIHMULLER, F. B., O'DELL, S. J. & MARSHALL, J. F. (1992) MK-801 protection against methamphetamine-induced striatal dopamine terminal injury is associated with attenuated dopamine overflow. Synapse 11, 155–163.PubMedGoogle Scholar
  133. WENGER, N. K., SPEROFF, L. & PACKARD, B. (1993) Cardiovascular health and disease in women. New England Journal of Medicine 329, 247–256.PubMedGoogle Scholar
  134. WIRZ-JUSTICE, A., HACKMANN, E. & LICHTSTEINER, M. (1974) The effect of estradiol dipropionate and progesterone on monoamine uptake in rat brain. Journal of Neurochemistry 22, 187–189.PubMedGoogle Scholar
  135. YOUNGSTER, S. K., NICKLAS, W. J. & HEIKKILA, R. E. (1989) Structure-activity study of the mechanisms of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity II. Evaluation of the biological activity of the pyridinium metabolites formed from the monoamine oxidase-catalyzed oxidation of MPTP analogs. Journal of Pharmacology and Experimental Therapeutics 249, 829–835.PubMedGoogle Scholar
  136. YU, Y.-L. & WAGNER, G. C. (1994) Influence of gonadal hormones on sexual differences in sensitivity to methamphetamine-induced neurotoxicity. Journal of Neural Transmission 8, 215–221.PubMedGoogle Scholar

Copyright information

© Kluwer Academic Publishers 2000

Authors and Affiliations

  • Dean E. Dluzen
    • 1
  1. 1.Department of AnatomyNortheastern Ohio Universities College of Medicine, (NEOUCOM)RootstownUSA

Personalised recommendations