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在母体免疫激活大鼠模型中对纹状体外多巴胺D2受体进行成像

Imaging extra-striatal dopamine D2 receptors in a maternal immune activation rat model.

作者信息

Oh-Nishi Arata, Nagai Yuji, Seki Chie, Suhara Tetsuya, Minamimoto Takafumi, Higuchi Makoto

机构信息

Department of Functional Brain Imaging, National Institutes for Quantum Science and Technology, Chiba, 263-8555, Japan.

Division of Immune-Neuropsychiatry, Faculty of Medicine, Shimane University, Shimane, 693-8501, Japan.

出版信息

Brain Behav Immun Health. 2022 Mar 11;22:100446. doi: 10.1016/j.bbih.2022.100446. eCollection 2022 Jul.

Abstract

Maternal immune activation (MIA) is a risk factor for schizophrenia in the offspring. MIA in pregnant rodents can be induced by injection of synthetic polyriboinosinic-polyribocytidilic acid (Poly I:C), which causes decreased striatal dopamine D2 receptor (D2R) expression and behavioral dysfunction mediated by the dopaminergic system in the offspring. However, previous studies did not determine whether Poly I:C induced cortical dopamine D2R abnormality in an MIA rat model. In this study, we performed micro-positron emission tomography (micro-PET) imaging and neurochemical analyses of cortical D2Rs in MIA. In the micro-PET analyses, the anterior cingulate cortex (ACC) region in the offspring showed significantly reduced binding potential for [C]FLB457, a high affinity radio-ligand toward D2Rs. Neurochemical analysis showed reduction of D2Rs and augmentation of dopamine turnover in the ACC of the rat offspring. Thus, MIA induces dopaminergic dysfunction in the ACC of offspring, similar to the neuronal pathology reported in patients with schizophrenia.

摘要

母体免疫激活(MIA)是后代患精神分裂症的一个风险因素。在怀孕的啮齿动物中,通过注射合成聚肌苷酸-聚胞苷酸(Poly I:C)可诱发MIA,这会导致后代纹状体多巴胺D2受体(D2R)表达降低以及由多巴胺能系统介导的行为功能障碍。然而,先前的研究并未确定在MIA大鼠模型中Poly I:C是否会诱发皮质多巴胺D2R异常。在本研究中,我们对MIA大鼠的皮质D2R进行了微型正电子发射断层扫描(micro-PET)成像和神经化学分析。在micro-PET分析中,后代的前扣带回皮质(ACC)区域对[C]FLB457(一种对D2R具有高亲和力的放射性配体)的结合潜能显著降低。神经化学分析显示,大鼠后代ACC中的D2R减少,多巴胺周转率增加。因此,MIA会诱发后代ACC中的多巴胺能功能障碍,这与精神分裂症患者报告的神经元病理学相似。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0ab/9043973/6af297ba72fa/gr1.jpg

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