Estrogen modulates responses of striatal dopamine neurons to MPP+:: evaluations using in vitro and in vivo techniques
Estrogen modulates responses of striatal dopamine neurons to MPP+:: evaluations using in vitro and in vivo techniques
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DOI：
10.1016/s0006-8993(00)02511-7
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发表时间：
2000-07-28
期刊：
影响因子：
2.9
通讯作者：
Leipheimer, RE
中科院分区：
文献类型：
--
作者：
Arvin, M;Fedorkova, L;Leipheimer, RE
采用体外灌注和体内电化学研究雌激素在调节 MPP+ 诱导的去势雌性大鼠纹状体和伏核多巴胺输出中的作用。对于体外灌注实验，使用 HPLC 和电化学检测方法，从用单独 MPP+ 或 MPP+ 与雌激素脉冲的克雷布林格磷酸盐缓冲液灌注纹状体片段来确定多巴胺和二羟基苯乙酸的释放。体内电化学实验记录了碳纤维微电极立体定向穿过纹状体和伏核的多巴胺信号。通过固定在电极上的玻璃微量移液器，单独或与雌激素结合 MPP+ 压力喷射，刺激多巴胺释放。与仅接受MPP+的腔室相比，接受MPP+与雌激素输注的灌流腔室的多巴胺输出显示显着较低的多巴胺输出。 MPP+输注后二羟基苯乙酸的输出量没有增加。电化学实验数据表明，雌激素显着降低了纹状体和伏隔核中 MPP+-evokrd 多巴胺信号的幅度和清除率。本研究的结果表明：(1) MPP+ 引起纹状体多巴胺释放，并且根据体内电化学和体外灌注测定，在雌激素存在的情况下，这种效应显着降低：(2) 根据体内电化学测定，在伏核中观察到类似但减弱的效应； (3)雌激素起到抑制纹状体和伏隔核中多巴胺清除的作用；(4)雌激素可以通过减少多巴胺能神经元对神经毒素的摄取而起到神经保护剂的作用。 (C) 2000 Elsevier Science B.V. 保留所有权利。
In vitro superfusion and in vivo electrochemistry were used to investigate the role of estrogen in modulatings MPP+-induced dopamine output in the corpus striatum and nucleus accumbens of ovariectomized female rats. For in vitro superfusion experiments, dopamine and dihydroxyphenylacetic acid release were determined using HPLC with electrochemical detection from superfusion of corpus striatum fragments with Kreb's ringer phosphate buffer pulsed with MPP+ alone or MPP+ with estrogen. The in vivo electrochemistry experiments recorded the dopamine signal from carbon fiber microelectrodes stereotaxically passed through the corpus striatum and nucleus accumbens. Dopamine release was stimulated by pressure ejection of MPP+ alone or in combination with estrogen through glass micropipettes fastened to the electrodes. Dopamine output from superfusion chambers which received infusion of MPP+ with estrogen showed significantly lower output of dopamine compared with chambers which received MPP+ alone. Outputs of dihydroxyphenylacetic acid did not increase following MPP+ infusions. Data from the electrochemistry experiments demonstrated that estrogen significantly reduced both the amplitude and clearance rates of the MPP+-evokrd dopamine signal in both the corpus striatum and nucleus accumbens. Results of this study demonstrate that: (1) MPP+ evokes striatal dopamine release and this effect is significantly reduced in the presence of estrogen as determined by both in vivo electrochemistry and in vitro superfusion: (2) similar, albeit attenuated effects are observed in the nucleus accumbens as determined with in vivo electrochemistry; (3) estrogen acts to inhibit the clearance of dopamine in both the striatum and nucleus accumbens: and (4) estrogen may function as a neuroprotectant by reducing the uptake of neurotoxin into dopaminergic neurons. (C) 2000 Elsevier Science B.V. All rights reserved.