Abstract
BACKGROUND: 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. METHODS: Immunohistochemistry of wild type and URAT1 knockout mouse brain using paraffin or frozen sections and a rabbit polyclonal anti-mouse URAT1 antibody were employed. RESULTS: 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. CONCLUSION: 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.