| Parkinson's disease (PD) represents an age-related movement disorder, which results from degeneration of the nigrostriatal dopaminergic system. Marked sex differences have been reported to occur in the incidence of PD, with male to female ratios ranging from 1.36~3.70 to1. Gonadal steroid hormones, in particular estrogen, have been shown to exert substantial modulatory effects upon nigrostriatal dopamine system, and it may likely contribute to the gender differences which exist in the incidence of PD. Moreover, recent research has reported that the amygdala undergoes severe pathological changes during the course of PD, and our former studies indicated that the maximum dopamine (DA) release from the central amygdala nucleus (CAN) evoked by electrical stimulation in the female rats was significantly higher than that in the male rats. In the present study, fast cyclic voltammetry was employed to monitor DA release from CAN of female rats which were ovariectomized (OVX) and/or treated with different doses of estradiol benzoate (EB). Radioimmunoassay was used to measure the serum estradiol concentration of the rats. And another method-high performance liquid chromatography-electrochemical detection (HPLC-ECD) was used to detect the contents of DA and its metabolites in the amygdala and striatum of the rats under different level of serum estradiol concentration. In addition, DA release was measured from CAN following electrical stimulation of ventral tegmental area (VTA) in the model rats of PD, in which medial forebrain bundle (MFB) was lesioned unilaterally with 6-hydroxydopamine (6-OHDA). The influence of EB on rotational behavior induced by apomorphine (APO) in ovariectomized PD rats was investigated. Our aim is to put forward new experimental evidence to explain the sex difference in the incidence of PD, and determine the effects of estrogen in PD. The results were as follows:1 DA release from CAN was significantly higher in EB-treated OVX rats compared to control OVX rats, and there was a dose-dependent relationship between DA release and the administered dosage of EB. EB(10μg/0.1ml oil/d and 20μg/0.1ml oil/d) can increase the DA release from CAN apparently, but no significant difference was observed although DA release of EB-treated (5μg/0.1ml oil/d) group was higher than that of the normal rats.2 The serum concentration of estradiol in OVX rats was comparative different after EB(5μg/0.1ml oil/d,10μg/0.1ml oil/d 20μg/0.1ml oil/d) or the vehicle (peanut oil 0.1ml) was administered subcutaneously.3 The correlationship between DA release from CAN and serum concentration of estradiol in rats was demonstrated, and the coefficient of correlation is 0.986.4 The contents of DA and its metabolites in Amy but not Str were significantly higher when the OVX rats were treated with high dose of estradial benzoated (EB). 5 The turnover rate of DA in Amy of the OVX rats was more lower than that of normal and EB-treated OVX rats.6 The turnover rate of DA in Amy was about twice the Str, while the content of DA in Amy was six times less the Str.7 DA release from CAN could hardly be measured in lesioned side of 6-OHDA PD rats, while DA release from un-lesioned side in PD rats was not affected.8 After the administration of EB(10μg/0.1ml oil/d) subcutaneously for 3 days and 7 days in OVX PD rats, DA release from CAN of both sides of PD rats was increased significantly, in particular the un-lesioned side, compared to the oil-treated group. 9 In the OVX PD rats, rotational behavior induced by APO was attenuated after EB was administered than before, and the difference of rotational numbers between EB-treated group and oil-treated group had statistic value. Taking the above results together, it suggests that estrogen play an important role in the regulation of DA release from mesolimbic dopamine system. Estrogen administered properly can increase the dopamine release as well as lower symptom severity in PD rats. Our data provides further experimental...
|
PDF Full Text Request