Estrogen alters MPTP-induced neurotoxicity in female mice: effects on striatal dopamine concentrations and release.
The effects of estrogen on MPTP-induced neurotoxicity of the nigrostriatal dopaminergic system were examined in C57Bl and CD-1 mice. Ovariectomized mice with and without estrogen were treated with MPTP or its vehicle. The effects of these treatments on striatal dopamine concentrations and L-DOPA-stimulated dopamine and L-3,4-dihydroxyphenylacetic acid (DOPAC) release in vitro were determined. Dopamine concentrations of C57Bl mice receiving estrogen before MPTP were significantly greater than those of non-estrogen-treated MPTP mice as well as estrogen-treated mice receiving the MPTP vehicle. Dopamine concentrations of the CD-1 mice did not differ with these treatments. L-DOPA-evoked dopamine release values of estrogen-treated C57Bl mice were significantly increased compared with non-estrogen-treated mice. No such differences were observed in the MPTP-treated C57Bl mice. DOPAC release rates were similar to that of dopamine in these C57Bl mice. In the CD-1 mice estrogen also produced a significant increase in L-DOPA-evoked dopamine release; however, this response was unaltered by MPTP treatment. A significant increase in L-DOPA-evoked DOPAC output was obtained only for estrogen-treated CD-1 mice. Both strains show very similar responses to the estrogen treatment, but differential responses of dopamine release to L-DOPA between the C57Bl and CD-1 mice were obtained with regard to the interactive effects of estrogen and MPTP. Our results suggest that in addition to its role as modulator, estrogen may also function as a neuroprotectant against MPTP neurotoxicity of the nigrostriatal dopaminergic system in the C57Bl mouse.
Dluzen
D E
DE
Department of Anatomy, Northeastern Ohio Universities College of Medicine, Rootstown 44272-0095, USA.
McDermott
J L
JL
Liu
B
B
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D007980:Levodopa / Q000494:pharmacology; D020267:MPTP Poisoning; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D009994:Osmolar Concentration; D010052:Ovariectomy
D015102:3,4-Dihydroxyphenylacetic Acid; D007980:Levodopa; D004958:Estradiol; D004298:Dopamine