However, the sparse localization of ER-_ seems sufficient to mediate estrogen neuroprotection in the striatum, as evidenced by the study of D’Astous et al. [138] who demonstrated that an ER-_ agonist (PPT) exerts protection against MPTPinduced dopamine depletion in the striatum, while ER-_ agonists (DPN, Delta-3-diol) were ineffective. This preliminary evidence suggests that estrogen protection in the striatum may involve ER-_, but additional studies such as examining estrogen ability to protect the striatum against MPTP-induced damage in ER-knockout mice would help add important corroborating evidence for the role of ER in estrogen action in the striatum. Furthermore, alternative pathways for estrogen neuroprotection must be considered as well, as work by Quesada and Micevych [141] has provided evidence that estrogen interacts with the IGF-1 system to protect nigrostriatal dopaminergic neurons and maintain motor function after 6- hydroxydopamine lesion animals. Finally, it should be added that estrogen has also been shown to reduce the dyskinetic effects produced by MPTP in monkeys, suggesting that estrogen’s beneficial effects on the dopaminergic system applies to higher species [142].
However, the sparse localization of ER-_ seems sufficient to mediate estrogen neuroprotection in the striatum, as evidenced by the study of D’Astous et al. [138] who demonstrated that an ER-_ agonist (PPT) exerts protection against MPTPinduced dopamine depletion in the striatum, while ER-_ agonists (DPN, Delta-3-diol) were ineffective. This preliminary evidence suggests that estrogen protection in the striatum may involve ER-_, but additional studies such as examining estrogen ability to protect the striatum against MPTP-induced damage in ER-knockout mice would help add important corroborating evidence for the role of ER in estrogen action in the striatum. Furthermore, alternative pathways for estrogen neuroprotection must be considered as well, as work by Quesada and Micevych [141] has provided evidence that estrogen interacts with the IGF-1 system to protect nigrostriatal dopaminergic neurons and maintain motor function after 6- hydroxydopamine lesion animals. Finally, it should be added that estrogen has also been shown to reduce the dyskinetic effects produced by MPTP in monkeys, suggesting that estrogen’s beneficial effects on the dopaminergic system applies to higher species [142].
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