Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Heinrich-Hoffmann-Str. 10, 60528, Frankfurt, Germany.
Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital of Würzburg, Margarete-Höppel-Platz 1, 97080, Würzburg, Germany.
J Neural Transm (Vienna). 2018 Jun;125(6):913-923. doi: 10.1007/s00702-018-1867-3. Epub 2018 Feb 27.
The distinct subgroup of the Ras family member 2 (DIRAS2) gene has been found to be associated with attention-deficit/hyperactivity disorder (ADHD) in one of our previous studies. This gene is coding for a small Ras GTPase with unknown function. DIRAS2 is highly expressed in the brain. However, the exact neural expression pattern of this gene was unknown so far. Therefore, we investigated the expressional profile of DIRAS2 in the human and murine brain. In the present study, qPCR analyses in the human and in the developing mouse brain, immunocytological double staining on murine hippocampal primary cells and RNA in situ hybridization (ISH) on brain sections of C57BL/6J wild-type mice, have been used to reveal the expression pattern of DIRAS2 in the brain. We could show that DIRAS2 expression in the human brain is the highest in the hippocampus and the cerebral cortex, which is in line with the ISH results in the mouse brain. During mouse brain development, Diras2 levels strongly increase from prenatal to late postnatal stages. Co-expression studies indicate Diras2 expression in glutamatergic and catecholaminergic neurons. Our findings support the idea of DIRAS2 as a candidate gene for ADHD as the timeline of its expression as well as the brain regions and cell types that show Diras2 expression correspond to those assumed to underlie the pathomechanisms of the disease.
我们之前的一项研究发现， Ras 家族成员 2（DIRAS2）基因的一个独特亚组与注意力缺陷/多动障碍（ADHD）有关。该基因编码一种具有未知功能的小 Ras GTPase。DIRAS2 在大脑中高度表达。然而，到目前为止，该基因的确切神经表达模式尚不清楚。因此，我们研究了 DIRAS2 在人类和鼠脑中的表达谱。在本研究中，我们使用 qPCR 分析人类和发育中的鼠脑、对鼠海马原代细胞进行免疫细胞化学双重染色以及对 C57BL/6J 野生型小鼠脑切片进行 RNA 原位杂交（ISH），以揭示 DIRAS2 在大脑中的表达模式。我们可以证明 DIRAS2 在人脑中的表达最高的是海马体和大脑皮层，这与在鼠脑中的 ISH 结果一致。在鼠脑发育过程中，Diras2 水平从产前到晚期产后阶段强烈增加。共表达研究表明，Diras2 表达于谷氨酸能和儿茶酚胺能神经元中。我们的发现支持 DIRAS2 作为 ADHD 候选基因的观点，因为其表达的时间进程以及表现出 Diras2 表达的脑区和细胞类型与假定的疾病发病机制的基础相对应。
