estradiol-3-benzoate and Parkinson-Disease

Estradiol (E2), in addition to its known hormone function, is a neuroactive steroid that has shown neuroprotective profile in several models of neurological diseases. The present study explores the antioxidant effect of β-estradiol-3-benzoate (EB) on the neurotoxicity elicited by MPP

Topics: 1-Methyl-4-phenylpyridinium; Animals; Behavior, Animal; Disease Models, Animal; Dopamine; Dopaminergic Neurons; Dose-Response Relationship, Drug; Estradiol; Lipid Peroxidation; Male; Neostriatum; Neuroprotective Agents; Parkinson Disease; Rats; Rats, Wistar

Estrogen increases methamphetamine (MA)-induced neurotoxicity within the impaired nigrostriatal dopaminergic (NSDA) system of ovariectomized female mice, as defined by enhanced striatal dopamine (DA) depletion. In this study we compared the effects of a lower dose of estradiol benzoate (EB, 1 microg) with related agents--tamoxifen (TMX, 12.5 microg), testosterone (5 microg) and dehydroepiandrosterone (DHEA, 3 mg) in this paradigm. In experiment 1, ovariectomized mice received an initial treatment with MA. At 1 week after MA, mice were treated with EB, TMX, testosterone, DHEA or oil vehicle and 24 h later a second MA treatment. Striatal DA and 3,4-dihydroxyphenylacetic acid (DOPAC) concentrations in the MA-treated groups were decreased compared to the non-MA-treated control. Neither EB nor any of the other agents tested showed enhanced neurodegenerative or neuroprotective effects against a second MA invasion. To verify that estrogen was capable of showing a neuroprotective effect under a condition of two administrations of MA, in experiment 2, EB was administered either once or twice prior to each of the two MA treatments. EB treatment prior to the first MA invasion or first and second MA protected the NSDA system against DA and DOPAC depletion. These results imply that a lower dose of EB, TMX, testosterone and DHEA cannot exert neurodegenerative or neuroprotective effects in the impaired NSDA model. However, EB administered prior to the introduction of neurotoxicity can protect the NSDA system. This study may provide an understanding of the variations in results on the effects of estrogen upon the NSDA neurodegenerative disorder, Parkinson's disease.

Topics: 3,4-Dihydroxyphenylacetic Acid; Androgens; Animals; Dopamine; Dopamine Agents; Dose-Response Relationship, Drug; Drug Administration Schedule; Estradiol; Estrogen Antagonists; Female; Methamphetamine; Mice; Neostriatum; Nerve Degeneration; Neuroprotective Agents; Neurotoxins; Ovariectomy; Parkinson Disease; Substantia Nigra; Tamoxifen