Estrogen as a neuromodulator of MPTP-induced neurotoxicity: effects upon striatal dopamine release.

Title

Estrogen as a neuromodulator of MPTP-induced neurotoxicity: effects upon striatal dopamine release.

Creator

Disshon K A; Dluzen D E

Publisher

Brain research

Date

1997
1997-08

Description

The effects of estrogen upon MPTP-induced neurotoxicity were examined using in vitro superfusion. In Experiment 1, striatal tissue from ovariectomized rats was infused with MPP+ (10 microM), a combination of MPP+ and 17beta-estradiol (300 nM), the same dose of estradiol preceding MPP+, or no treatment infusion. The effects of these treatments on dopamine release rates during the infusion periods were determined. Infusion of MPP+ resulted in a significant increase in dopamine release as compared to the control. Estradiol added to the MPP+ infusion significantly attenuated this dopamine (DA) release, while estradiol treatment preceding the MPP+ had no effect. In Experiment 2, three different doses 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 release. In Experiment 3, estradiol alone (300 nM) was infused, to determine dopamine release rate effects of the hormone itself. There was no difference between estradiol treated and non-infused control groups. These results demonstrate that the gonadal steroid hormone estradiol can 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-dependent, 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 may represent an important variable responsible for the sex differences which are reported in Parkinson's disease.

Subject

*MPTP Poisoning; 1-Methyl-4-phenylpyridinium/toxicity; Animals; Dopamine Agents/*toxicity; Dopamine/*metabolism; Estradiol/pharmacology; Estrogens/*physiology; Female; Neostriatum/drug effects/*metabolism; Neurotransmitter Agents/*physiology; Ovariectomy; Rats; Sprague-Dawley

Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Pages

9–16

Issue

1

Volume

764

Citation

Disshon K A; Dluzen D E, “Estrogen as a neuromodulator of MPTP-induced neurotoxicity: effects upon striatal dopamine release.,” NEOMED Bibliography Database, accessed September 22, 2021, https://neomed.omeka.net/items/show/3838.

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