Elsevier

Neuroscience

Volume 130, Issue 2, 2005, Pages 369-382
Neuroscience

Effects of neonatal and prepubertal hormonal manipulations upon estrogen neuroprotection of the nigrostriatal dopaminergic system within female and male mice

https://doi.org/10.1016/j.neuroscience.2004.09.033Get rights and content

Abstract

Estrogen (E) can function as a neuroprotectant of the nigrostriatal dopaminergic (NSDA) system against methamphetamine (MA) neurotoxicity in female, but not male, mice. In the present report we examined whether the organizational effects of gonadal steroid hormones, as exerted in the early postnatal period, or developmental effects, as exerted during the pubertal period, would contribute to this sexually dimorphic neuroprotectant action of E. Neonatal gonadectomy and treatment with testosterone of female mice, retained the ability to show an E neuroprotectant response when tested as adults. However, females not treated with gonadal steroids failed to show an E-dependent neuroprotectant response. Neonatal gonadectomy of male mice, failed to result in the display of an E neuroprotectant response when tested as adults. Prepubertal gonadectomy of female mice, with or without testosterone treatment, abolished the capacity for E to produce neuroprotection against MA-induced NSDA neurotoxicity. Nor did prepubertal gonadectomy enable male mice to show an E neuroprotectant response. Taken together these results demonstrate that none of the manipulations performed within male mice enabled them to show an E-dependent neuroprotective response against MA-induced neurotoxicity of the NSDA system when tested as adults. For the female, it appears that the presences of gonadal steroids at these two developmental periods are needed for the display of an E-dependent neuroprotectant response within the adult.

Section snippets

General procedure

Two experiments were performed as part of this report. In experiment 1, the effects of neonatal hormonal manipulations were examined, while the effects of prepubertal hormonal manipulations were performed in experiment 2. The purpose of experiment 1 was to examine whether attempts to masculinize the neonatal female or feminize the neonatal male mouse would alter the sexually dimorphic effects of E to function as a neuroprotectant within the adult. Masculinization of the female was achieved by

Experiment 1

A summary of the data obtained from attempts to masculinize the female mouse with neonatal treatments of T is presented in Fig. 1. Substantial reductions in striatal DA concentrations (Fig. 1A) and increases in DOPAC/DA ratios (Fig. 1B) are observed in MA versus vehicle treated mice demonstrating the neurotoxic effects of this psychostimulant. No statistically significant differences in either striatal DA concentrations or DOPAC/DA ratios were obtained between E- versus non-E-treated mice that

Discussion

The present results reveal some interesting organizational and developmental influences of gonadal steroid hormones upon the capacity for E to function as a neuroprotectant within the adult. The basic premise for this experiment was that a sexually dimorphic difference exists in E's capacity to function as a neuroprotectant and the issue of whether this difference may be attributed to organizational or developmental actions of gonadal steroid hormones was addressed. To this end we attempted to

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