Ovariectomy and estradiol treatment affect the dopamine transporter and its gene expression in the rat brain
Ovariectomy and estradiol treatment affect the dopamine transporter and its gene expression in the rat brain
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DOI：
10.1016/s0169-328x(97)00082-x
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发表时间：
1997-06-01
期刊：
影响因子：
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通讯作者：
DiPaolo, T
中科院分区：
文献类型：
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作者：
Bosse, R;Rivest, R;DiPaolo, T
研究了性腺激素戒断和雌激素治疗对大鼠多巴胺转运蛋白（DAT）的影响。短期卵巢切除（ST-OVX，2周）和长期卵巢切除（LT-OVX，3个月）大鼠治疗或不与17 β-雌二醇（E-2）2周。通过原位杂交测定黑质纹状体通路的黑质背侧部（SNc）和中脑边缘通路的腹侧被盖区（VTA）的DAT mRNA表达，而通过[H-3]GBR-12935放射自显影术分别评估纹状体和中脑核中的DAT水平。卵巢切除术产生的DAT密度在纹状体和脑桥核的时间依赖性降低和E-2治疗没有显着恢复这些DAT水平。ST-OVX和E-2处理ST-OVX动物均未改变SNc和VTA中DAT mRNA的表达。然而，LT-OVX动物在这些区域显示DAT mRNA水平增加。LT-OVX动物的E-2治疗部分恢复了SNc中的DAT mRNA水平，并使VTA中的这些水平保持不变。OVX诱导的DAT密度及其mRNA水平的这些相反的变化表明非基因组机制的参与，如转录后事件和/或膜效应。性腺激素戒断后神经递质的改变可能导致易感妇女绝经期发生的CNS疾病，卵巢切除大鼠构成了研究绝经后神经递质平衡变化的有用模型。
The impact of gonadal hormone withdrawal and estrogen therapy was investigated on the rat dopamine transporter (DAT). Short-term ovariectomized (ST-OVX, 2 weeks) and long-term ovariectomized (LT-OVX, 3 months) rats were treated or not with 17 beta-estradiol (E-2) for 2 weeks. DAT mRNA expression was measured by in situ hybridization in the substantia nigra pars compacta (SNc) for the nigrostriatal pathway and the ventral tegmental area (VTA) for the mesolimbic pathway whereas DAT levels were assessed by [H-3]GBR-12935 autoradiography, respectively, in the striatum and the nucleus accumbens. Ovariectomy produced a time-dependent decrease of the DAT density in the striatum and the nucleus accumbens and the E-2 treatment did not significantly restore these DAT levels. Neither ST-OVX nor E-2 treatment of the ST-OVX animals altered the DAT mRNA expression in the SNc and the VTA. However, LT-OVX animals showed increased DAT mRNA levels in these regions. E-2 treatment of LT-OVX animals partially restored DAT mRNA levels in the SNc and left these levels unchanged in the VTA. These opposite variations induced by OVX on the DAT density and their mRNA levels suggest the involvement of non-genomic mechanisms, such as post-transcriptional events and/or membrane effects. Altered neurotransmission following gonadal hormone withdrawal may contribute to CNS disorders occurring at menopause in predisposed women, Ovariectomized rats constitute a useful model to study the changes in neurotransmitters balance occurring after menopause.