Estrogen as a neuroprotectant against MPTP-induced neurotoxicity in C57/B1 mice.

Castrated retired breeder male and female mice were treated or not with a 17 beta-estradiol pellet. At 10 days postcastration +/- estrogen treatment all animals were treated with MPTP. Five days later, concentrations of dopamine were determined from the corpus striatum and olfactory tubercle. Both castrated male and female mice treated with estrogen had significantly greater concentrations of dopamine within the corpus striatum compared with their respective gender controls, which did not receive estrogen. By contrast, no statistically significant differences in olfactory tubercle dopamine concentrations were obtained. Overall concentrations of dopamine within the corpus striatum, but not olfactory tubercle, were substantially greater in female vs. male mice. These data demonstrate that treatment with estrogen prevents reductions in corpus striatal dopamine concentrations in castrated mice treated with MPTP. Interestingly, this effect of estrogen was observed in both male and female mice. These results suggest that estrogen may serve as a neuroprotectant against an agent that is toxic to the nigrostriatal dopaminergic system in both male and female animal models of Parkinsonism.