Department of Human Physiology and Pathology, Faculty of Pharma-Sciences, Teikyo University, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan.
Fluids Barriers CNS. 2013 Oct 24;10(1):31. doi: 10.1186/2045-8118-10-31.
Elevated uric acid (UA) is commonly associated with gout and it is also a known cardiovascular disease risk factor. In contrast to such deleterious effects, UA possesses neuroprotective properties in the brain and elucidating the molecular mechanisms involved may have significant value regarding the therapeutic treatment of neurodegenerative disease. However, it is not yet fully established how UA levels are regulated in the brain. In this study, we investigated the distribution of mouse urate transporter 1 (URAT1) in the brain. URAT1 is a major reabsorptive urate transporter predominantly found in the kidney.
Immunohistochemistry of wild type and URAT1 knockout mouse brain using paraffin or frozen sections and a rabbit polyclonal anti-mouse URAT1 antibody were employed.
Antibody specificity was confirmed by the lack of immunostaining in brain tissue from URAT1 knockout mice. URAT1 was distributed throughout the ventricular walls of the lateral ventricle, dorsal third ventricle, ventral third ventricle, aqueduct, and fourth ventricle, but not in the non-ciliated tanycytes in the lower part of the ventral third ventricle. URAT1 was localized to the apical membrane, including the cilia, of ependymal cells lining the wall of the ventricles that separates cerebrospinal fluid (CSF) and brain tissue.
In this study, we report that URAT1 is expressed on cilia and the apical surface of ventricular ependymal cells. This is the first report to demonstrate expression of the urate transporter in ventricular ependymal cells and thus raises the possibility of a novel urate transport system involving CSF.
尿酸(UA)升高通常与痛风有关,也是已知的心血管疾病危险因素。与这种有害影响相反,UA 在大脑中具有神经保护特性,阐明相关的分子机制对于神经退行性疾病的治疗可能具有重要价值。然而,UA 在大脑中的水平如何调节还不完全清楚。在这项研究中,我们研究了小鼠尿酸转运蛋白 1(URAT1)在大脑中的分布。URAT1 是一种主要的尿酸重吸收转运蛋白,主要存在于肾脏中。
使用石蜡或冷冻切片对野生型和 URAT1 敲除小鼠的大脑进行免疫组织化学染色,并使用兔多克隆抗小鼠 URAT1 抗体。
抗体特异性通过 URAT1 敲除小鼠脑组织中缺乏免疫染色得到证实。URAT1 分布于侧脑室、背侧第三脑室、腹侧第三脑室、导水管和第四脑室的室壁,但不在腹侧第三脑室下部无纤毛的室管膜下细胞中。URAT1 定位于脑室壁衬里的室管膜细胞的顶膜,包括纤毛。脑室壁将脑脊液(CSF)与脑组织分开。
在这项研究中,我们报告 URAT1 表达于纤毛和脑室室管膜细胞的顶膜。这是首次报道尿酸转运蛋白在脑室室管膜细胞中表达,因此提出了一种涉及 CSF 的新型尿酸转运系统的可能性。