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Keywords:

  • 17β-estradiol;
  • 17α-estradiol;
  • MPTP;
  • dopamine;
  • dopamine transporter;
  • striatum

Abstract

Neuroprotective activity of estrogens is reported in Alzheimer disease and recently has also been suggested for Parkinson disease, a disease affecting more men than women. To characterize this estrogenic activity, we studied the effects of 17β- and 17α-estradiol treatment (1 μg twice daily 5 days before, during the day of four MPTP (15 mg/kg) injections, and for the following 5 days) on dopamine striatal toxicity induced by the neurotoxin MPTP in retired breeder male C57BL/6 mice. Striatal dopamine concentrations and its metabolites dihydroxyphenylacetic acid and homovanillic acid measured by HPLC in MPTP mice that received 17β-estradiol were comparable to control animals, whereas MPTP mice treated with saline or 17α-estradiol showed important decreases of dopamine and its metabolites. Striatal serotonin and its metabolite 5-hydroxyindoleacetic acid concentrations remained unchanged after MPTP and treatments with steroids. Striatal [3H]GBR 12935 binding autoradiography to the dopamine transporter was as extensively decreased and correlated with dopamine depletion in MPTP mice, whereas this transporter mRNA decrease in the substantia nigra pars compacta was less pronounced. Treatment with steroids did not significantly change [3H]GBR 12935 binding, whereas dopamine transporter mRNA levels were not significantly different from controls. Under the present paradigm in retired breeder male mice, our results show dopaminergic and stereospecificity of estradiol to augment dopamine levels in MPTP-lesioned mice without protecting against the extensive loss of dopamine terminals and moderate cell body loss. Synapse 37:245–251, 2000. © 2000 Wiley-Liss, Inc.