ESTROGEN AS A NEUROMODULATOR OF MPTP-INDUCED NEUROTOXICITY - EFFECTS UPON STRIATAL DOPAMINE RELEASE

The effects of estrogen upon MPTP-induced neurotoxicity were examined using in vitro superfusion. In Experiment 1, striatal tissue from ovar iectomized rats was infused with MPP+ (10 mu M), a combination of MPP and 17 beta-estradiol (300 nM), the same dose of estradiol preceding MPP+, or no treatment infusion. The effects of these treatments on dop amine release rates during the infusion periods were determined. Infus ion of MPP+ resulted in a significant increase in dopamine release as compared to the control. Estradiol added to the MPP+ infusion signific antly attenuated this dopamine (DA) release, while estradiol treatment preceding the MPP+ had no effect. In Experiment 2, three different do ses of estradiol (0.3, 3, or 300 nM) were infused simultaneously with the MPP+. Doses of estradiol below 300 nM did not attenuate the DA rel ease. In Experiment 3, estradiol alone (300 nM) was infused, to determ ine dopamine release rate effects of the hormone itself. There was no difference between estradiol treated and non-infused control groups. T hese results demonstrate that the gonadal steroid hormone estradiol ca n modulate responses of striatal dopamine neurons to MPP+ by altering the immediate increase in dopamine release which occurs in response to this neurotoxin. These modulating effects of estradiol are dose-depen dent, and represent a direct effect upon striatal neurons, most likely involving a non-genomic mechanism of action. These results implicate that hormonal modulation of nigrostriatal dopaminergic neurotoxicity m ay represent an important variable responsible for the sex differences which are reported in Parkinson's disease. (C) 1997 Elsevier Science B.V.