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[Abstract] Objective To investigate the ultrastructural changes of hippocampus in urea transporter B (UT-B) null mice and the alterations of distribution and expression level of aquaporin 4 (AQP4) in brain, and to discuss the relationship between AQP4 expression changes and depression-like behaviors in UT-B null mice. Methods Behavior differences of wild-type and UT-B null mice(10 in each group) were detected with sucrose preference and forced swimming test. The ultrastructural changes of hippocampus were observed by transmission electron microscopy (TEM). Immunohistochemistry and Western blotting were performed to detect the distribution and expression level of AQP4 in both genotypes. Results The sucrose preference index of wild-type mice and UT-B null mice were (84. 67 ± 1. 62)% and (65. 67±2. 66)%, respectively (P<0. 001). The immobility time of forced swimming was (209. 1±7. 00) seconds and (128. 6±3. 75) seconds respectively (P<0. 001). The two behavioral test results showed that UT-B null mice exhibited depression-like behavior. TEM results displayed the abnormal neurons with swelling of myelinated and unmyelinated fibers and degenerative changes, and perivascular astrocyte end-feet swelling. Immunohistochemistry results showed AQP4-immunoreactive (IR) cells were significantly reduced in cortex, hippocampus and thalamus. AQP4-IR cells were distributed in the pia matter, ependymal and cerebrovascular, but the perivascular immunostaining decreased. Western blotting analysis showed that the expression level of AQP4 in hippocampus was down-regulated by 27. 1% (P< 0. 05). Conclusion Reduced expression of AQP4 in the cerebral cortex and hippocampus of UT-B null mice might induce depressive behaviors by inference neurogenesis and cerebral metabolism.
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Objective: To investigate the effect of high salt diet on the arterial blood pressure in the urea transporter B (UT-B) gene depletion (UT-B-/-) mice, and to clarify the possible mechanism of the UT-B-/- leading to the changes in the arterial blood pressure of the mice. Methods: The heterozygous (UT-B/-) mice were mated to obtain the wild-type (UT-B1/) and UT-B-/- mice with the same genetic background. The 4-week-old male UT-B1/1 and UT-B-/- mice were selected and fed on normal diet (0. 3% NaCl) or high salt diet (8. 0% NaCl) for 4 weeks. The mice were divided into UT-B/1 mice + normal diet (UT-B /1 +N) group, UT-B-/- mice + normal diet (UT-B-/- +N) group, UT-B1/1 mice+high salt diet (UT-B /1 +H) group, and UT-B-/- mice + high salt diet (UT-B-/- +H) group. The changes in water intakes and mean arterial pressures of the mice in various groups were monitored; RT-PCR, Western blotting and immunohistochemistry were used to detect the expression levels and location of UT-B mRNA and protein in choroid plexus (CP) of the brain tissue of the mice. The levels of serum angiotensin II (Ang II) and the Na levels in cerebrospinal fluid of the mice in various groups were determined by ELISA. Results: The PCR results of genomic DNA of mouse tail showed that there was a 400 bp base fragment in the UT-B mice, 250 and 400 bp base fragments in the UT-B mice, and 250 bp base fragment in the UT-B- - mice. Compared with normal salt diet group, the water intake of the mice in high salt diet was significantly increased (P<0. 01); compared with UT-B-/- +N group and UT-B1/1 + H group, the mean arterial pressure of the mice in UT-B-/- +H group was significantly increased (P<0. 01). The UT-B mRNA and protein expressed in the epithelial cells of CP in the UT-B/1 mice. Compared with UT-B-/- +N group and UTS1/ mice+H group, the Ang II level in serum of the mice in UT-B-/- mice+H group was significantly increased (P< 0.01); the Na level in cerebrospinal fluid of the mice was significantly increased (P< 0. 05). Conclusion: High salt diet can cause a significant increase in the mean arterial pressure in the UT-B-/- mice, and its mechanism is related to increasing the serum Ang II level and the Na' level in cerebrospinal fluid in the mice.
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Objective:To detect the expressions of urea transporter B (UT-B) in tumor tissue of bladder cancer patients and normal urothelium tissue, and to investigate its clinical significance of expression in bladder cancer tissue.Methods: Fifty-two paraffin-embedded specimens of bladder cancer patients and 15 normal urothelium specimens were selected. The expression levels of UT-B protein were detected by immunohistochemistry method.The difference of expression of UT-B in bladder cancer tissue and normal urothelium tissue and its relationship with the clinicopathological parameters were analyzed.Results:The expression rate of UT-B protein in bladder cancer tissue was 44.2%, while it was significantly higher in control group (93.3%), and the difference between two groups was significant (P=0.001).The positive expression rates of UT-B in bladder cancer tissue were significantly decreased with the increasing of histological grades, and there were significant differences between different grade groups (P=0.010).The positive expression rate of UT-B in muscle-invasive stage (Ta+T1) was significantly lower than that in non-muscle-invasive stage (T2+T3) (P=0.014).Conclusion:The reduction or lack of UT-B expression may promote the incidence, progression and invasiveness of bladder cancer.