5/6 nephrectomy (5/6Nx) effect on the brain

Chronic kidney disease (CKD) is a very important problem in global health treatment. CKD increases the disease risk of apoplexy, cardiac failure and cardiac infarction. In addition, neurological complications, including depression and restless legs syndrome, occur in almost all CKD patients; however, the mechanisms of these neurological complications remain unclear. Here, we showed the disruptive effect of chronic renal failure in 5/6 nephrectomy mice on an immobility time of forced swim and tail suspension test and the 24-hr rhythm of Drd2 and clock gene expressions in the striatum. These disruptive effects were induced by abnormal signal transduction in high TGF-β1 expression from the kidney. Abnormal TGF-β signal in the striatum led to TCF7L2 expression and ID2 induced by TCF7L2 led to disruption of the 24-hr rhythm of clock gene expression. These findings suggest that neurological complications in CKD might be overcome by amelioration of the TGF-β signal. Differential gene expression between 5/6 nephrectomized and sham-operated mouse was measured on the brain.