Research Paper Volume 15, Issue 20 pp 10972—10995

Chronic kidney disease causes blood-brain barrier breakdown via urea-activated matrix metalloproteinase-2 and insolubility of tau protein

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Figure 1. Chronic kidney disease causes loss of spatial working memory in mice. (A) Establishment of a CKD model in mice by providing wild-type C57BL/6JJcl mice a diet containing 0.20% adenine for six weeks. (B) Masson’s Trichrome staining showed tubulointerstitial fibrosis and diffuse tubular dilations in the kidneys of adenine-treated mice. Scale bar, 500 μm. (C) Serum urea nitrogen and creatinine, indicating uremic solutes, were elevated in CKD (n = 6 for each group). (D) The protein expression levels of α-smooth muscle actin (α-SMA) and fibronectin with cleaved fibronectin were elevated in the kidney tissues of CKD mice (n = 4 for each group). (E) We performed the novel object recognition test. The discrimination index, which represents a spatial reference memory, was significantly decreased in the CKD group compared with the control group (n = 19 in the control group; n = 18 in the CKD group). (F) The percentages of spontaneous alternation in the Y-maze test were not significantly different between the two groups (n = 12 in the control; n = 10 in the CKD group, respectively). Data are presented as mean ± standard deviation of the mean. Normality was assessed with the Shapiro–Wilk test. Statistical significance between the two groups was evaluated using an unpaired t test. P < 0.05 was considered statistically significant. CKD, chronic kidney disease.