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首页> 外文期刊>The European Journal of Neuroscience >Preferential alterations in the mesolimbic dopamine pathway of heterozygous reeler mice: an emerging animal-based model of schizophrenia.
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Preferential alterations in the mesolimbic dopamine pathway of heterozygous reeler mice: an emerging animal-based model of schizophrenia.

机译：杂合性绕线小鼠的中脑边缘多巴胺途径的优先改变：基于精神分裂症的新兴动物模型。

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Based on a number of neuroanatomical and behavioural similarities, recent evidence suggests that heterozygous reeler mice, haploinsufficient for reelin expression, represent a useful model of psychosis vulnerability. As brain mesolimbic dopamine pathways have been proposed to be associated with the pathophysiology of psychotic disorders, we thought it would be of interest to examine whether these animals present disturbances in the mesolimbic dopamine system. To this end we studied by immunocytochemical, in situ hybridization procedures and receptor autoradiography, several markers of the mesotelencephalic dopamine pathway in heterozygous reeler mice and controls. We report that heterozygous reeler mice exhibit a reduction in the number of tyrosine hydroxylase-immunoreactive cell bodies and tyrosine hydroxylase mRNA levels in the ventral tegmental area, as well as a reduction of tyrosine hydroxylase and dopamine transporter immunoreactivity in the dopamine terminal fields of the limbic striatum. In these areas we also observed a reduction of dopamine D2 receptor mRNA. Finally, a marked increase in D3 receptor mRNA levels was observed concomitant with a significant increase in D3 binding sites. On the contrary, the nigrostriatal pathway did not show any significant alteration in heterozygous reeler mice with regards to the dopaminergic markers examined in substantia nigra cell bodies and dorsal striatum dopamine terminal fields. These results suggest a specific link between reelin-related neuronal pathology and dopamine involvement in the pathophysiology of psychotic disorders.
机译：基于许多神经解剖学和行为上的相似性，最近的证据表明，杂合的卷轴小鼠，单核细胞不足以表达reelin，代表了精神病易感性的有用模型。由于脑中脑边缘多巴胺途径已被提出与精神病性疾病的病理生理相关，我们认为研究这些动物是否在中脑边缘多巴胺系统中出现紊乱很有意义。为此，我们通过免疫细胞化学，原位杂交程序和受体放射自显影研究了杂合绕线器小鼠和对照中脑脑多巴胺途径的几种标记。我们报告杂合reeler小鼠减少腹侧被盖区酪氨酸羟化酶免疫反应性细胞体的数量和酪氨酸羟化酶mRNA水平的减少，以及减少边缘区多巴胺末端区域的酪氨酸羟化酶和多巴胺转运蛋白的免疫反应性纹状体。在这些区域，我们还观察到多巴胺D2受体mRNA的减少。最后，观察到D3受体mRNA水平显着增加，同时D3结合位点显着增加。相反，在黑质实质细胞体和背侧纹状体多巴胺末端区域中检测到的多巴胺能标志物方面，杂合性绕线小鼠中黑质纹状体途径未显示任何显着改变。这些结果表明，瑞林相关神经元病理学与多巴胺参与精神病性疾病的病理生理学之间存在特定联系。

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