Estrogen decreases corpus striatal neurotoxicity in response to 6-hydroxydopamine

doi:10.1016/S0006-8993(97)00630-6

Brain Research

Volume 767, Issue 2, 5 September 1997, Pages 340-344

https://doi.org/10.1016/S0006-8993(97)00630-6 Get rights and content

Abstract

Ovariectomized rats treated or not with an estradiol pellet were subjected to an unilateral intrastriatal infusion of 6-hydroxydopamine (6-OHDA). Various parameters of nigrostriatal dopaminergic function as derived from measurements of dopamine and dihydroxyphenylacetic acid (DOPAC) concentrations were determined from the 6-OHDA lesioned and non-lesioned sides of the corpus striatum in these animals. Dopamine concentrations within the 6-OHDA lesioned striatum of estrogen-treated rats were significantly greater than non-estrogen-treated rats. There were no differences in striatal dopamine concentrations between estrogen- versus non-estrogen-treated rats on their non-lesioned side. In contrast to that of dopamine, no differences in DOPAC concentrations between estrogen and non-estrogen-treated rats were obtained within the 6-OHDA-lesioned side. The DOPAC concentrations on the non-lesioned side of the striatum were significantly greater in the non-estrogen-treated rats. These results demonstrate that estrogen significantly diminishes the depletion of striatal dopamine resulting from the neurotoxin 6-OHDA. The data obtained from the DOPAC determinations imply that this capacity of estrogen may be exerted through actions upon uptake processes of striatal dopaminergic neurons. Such findings suggest that estrogen may function as an important modulatory factor capable of attenuating degeneration within the corpus striatum, and in this way serve as a neuroprotectant of the nigrostriatal dopaminergic system.

Introduction

Within the central nervous system the gonadal steroid hormone estrogen is most notably associated with controlling hypothalamic functions involved with reproduction 14, 22. However, data from a variety of sources have demonstrated that the actions of estrogen in the brain are not limited to the hypothalamus and reproductive processes. Estrogen has been shown to exert substantial modulatory effects upon the nigrostriatal dopaminergic system [28]. For example, estrogen reduces striatal dopamine (DA) contents 12, 26 and restores DA turnover in the corpus striatum (STR) of ovariectomized female rats [4]. Moreover, basal and stimulated release of DA is increased from the STR of estrogen-treated rats 1, 2, 20, 21.

We have some recent evidence indicating that in addition to its effects upon these parameters of nigrostriatal DA function, estrogen may also play an important role in modulating responses to neurotoxins. Specifically, it has been shown that gonadectomized mice treated with estrogen showed attenuated STR DA depletions in response to the nigrostriatal DA neurotoxin, MPTP [11]. This effect was observed in both male and female mice and appears to represent a specific response to estrogen since replacement with testosterone to castrated males failed to prevent any MPTP-induced reductions in STR DA concentrations [9]. These findings demonstrate that estrogen can function as an important modulator of MPTP neurotoxicity within the mouse. The present report represents an attempt to further evaluate the potential for estrogen to act as a neuroprotectant of the nigrostriatal DA system. To accomplish this goal the effects of estrogen treatment upon striatal DA depletion resulting from 6-hydroxydopamine (6-OHDA) was studied in the female rat. Like that of the MPTP-treated mouse, the 6-OHDA-treated rat has served as a model of Parkinson's disease [15], and therefore we will evaluate whether estrogen's modulatory effects upon nigrostriatal DA neurotoxicity will be present in this model.

Section snippets

Animals

Fourteen adult female Sprague-Dawley rats (225–275 g) were used as subjects in the present experiments. All animals were housed individually in plastic cages under a 12:12 h light/dark cycle (lights on at 06.00 h). Lab chow and water were available ad libitum. All treatments used in this experiment adhere to the NIH guide for the Care and Use of Laboratory Animals and were approved by the Animal Care committee at NEOUCOM. The females were ovariectomized while under ketamine:acepromazine (10:1

Results

For one of the non-estrogen-treated animals DA concentrations from the 6-OHDA lesioned side (10 437 pg/mg) indicated an absence of any effect of the 6-OHDA as compared with levels obtained on the non-infused control side (11 775 pg/mg) and therefore the data of this animal was eliminated from the analyses. Pituitary weights of the estrogen-treated rats (mean±S.E.M.: 19.0±3.1 mg, n=6) were significantly greater (t=2.18, P<0.025) than that of rats not receiving estrogen (12.3±1.1 mg, n=7).

Discussion

The significantly greater bioassay measures of pituitary and uterine weights in the estrogen-treated rats confirmed that the estradiol pellets were effective. Associated with these peripheral endocrine effects of estrogen were some very distinct interactive effects between estrogen and 6-OHDA within the nigrostriatal DA system in the female rats. While the 6-OHDA treatments clearly exerted a neurotoxic effect within the STR, reducing STR DA concentrations to approximately 30% of contralateral

Acknowledgements

This work was in part supported by a grant from the National Institutes of Health.

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Research reportEstrogen decreases corpus striatal neurotoxicity in response to 6-hydroxydopamine

Abstract

Introduction

Section snippets

Animals

Results

Discussion

Acknowledgements

Behav. Brain Res.

Lancet

Psychoneuroendocrinology

Eur. J. Pharmacol.

Brain Res.

Neurotox. Teratol.

Neurosci. Lett.

Brain Res.

Brain Res. Bull.

Neurosci. Lett.

Brain Res.

Exp. Neurol.

Biochem. Pharmacol.

Brain Res. Bull.

Research report
Estrogen decreases corpus striatal neurotoxicity in response to 6-hydroxydopamine