Functional alterations of the nigrostriatal dopamine system in estrogen receptor-α knockout (ERKO) mice
Functional alterations of the nigrostriatal dopamine system in estrogen receptor-α knockout (ERKO) mice
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DOI：
10.1016/j.psyneuen.2008.03.007
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发表时间：
2008-07-01
影响因子：
3.7
通讯作者：
Beyer, Cordian
中科院分区：
文献类型：
--
作者：
Kueppers, Eva;Krust, Andre;Beyer, Cordian
雌激素是黑质纹状体多巴胺系统发育和功能的重要因素。雌激素还控制黑质纹状体多巴胺能系统的性别特异性分化和活性。我们使用了雌激素受体α基因敲除（-/-）模型（ERKO），研究这种特殊的受体亚型对男性和女性黑质纹状体多巴胺系统的功能特性的调节的影响。在纹状体水平，我们发现多巴胺D1受体（D1）和多巴胺受体相互作用蛋白78（Drip 78）的性别特异性调节。在雌性（-/-）小鼠中，与野生型（wt）动物相比，D1受体表达水平增加，而在雄性（-/-）小鼠中，与wt相比，Drip 78 mRNA水平降低。在中脑，酪氨酸羟化酶（TH）和脑源性神经营养因子（BDNF）的表达减少（-/-）小鼠的两种性别。胶质细胞源性神经营养因子（GDNF）的表达没有受到影响。这些数据表明，雌激素受体-α（ER α）信号的完整性是必要的蛋白质的基因表达的调节是重要的黑质纹状体系统在突触后纹状体和突触前中脑水平的功能。(c)2008爱思唯尔有限公司保留所有权利。
Estrogen represents an important factor for the development and function of the nigrostriatal dopamine system. Estrogen also controls sex-specific differentiation and activity of the nigrostriatal dopaminergic system. We used an estrogen receptor-alpha knockout (-/-) model (ERKO) to study the influence of this particular receptor subtype on the regulation of functional characteristics of the male and female nigrostriatal dopamine system. On the striatal level, we found a sex-specific regulation of dopamine D1 receptors (D1) and dopamine receptor-interacting protein 78 (Drip78). In female (-/-) mice D1 receptor expression levels were increased compared to wild type (wt) animals, whereas in male (-/-) mice Drip78 mRNA levels were decreased compared to wt. In the midbrain, expression of tyrosine hydroxylase (TH) and brain-derived neurotrophic factor (BDNF) was reduced in (-/-) mice of both sexes. Glial cell line-derived neurotrophic factor (GDNF) expression was not affected. These data demonstrate that the integrity of estrogen receptor-alpha (ER alpha) signalling is necessary for the regulation of gene expression of proteins known to be important for the function of the nigrostriatal system at the postsynaptic striatal and presynaptic midbrain level. (c) 2008 Elsevier Ltd. All rights reserved.