Effect Of Vitamin D On Cognitive Function In Mice With Chronic Kidney Disease

Background and ObjectiveChronic kidney disease（CKD）is a serious harm to human health,and its prevalence is increasing year by year.Cognitive dysfunction is common in CKD patients,mainly manifested as significantly reduced performance on attention,language,concept formation and reasoning,memory,executive function,and overall cognition test.Cognitive decline reduces the quality of life and increases the risk of death in patients with CKD.Vitamin D is a fat-soluble vitamin with rich biological properties.Studies have found that the reduction of vitamin D level is related to cognitive decline in CKD,but there is a lack of reports on the effect of vitamin D on cognitive function in CKD animals.Here,an animal model of CKD induced by adenine feeding was designed to explore the effect of vitamin D on cognitive function in CKD mice and its possible mechanism.MethodsMale C57BL/6J mice were selected as experimental subjects,a total of fifty-six mice were randomly divided into the following five groups: control（CON）group,model（CKD）group,and low,medium and high vitamin D（LVD,MVD and HVD）supplement group,including eight mice in CON group and twelve mice in each of the remaining four groups.The renal failure were induced in mice by feeding with 0.2%adenine diet for five weeks.After five weeks,all mice intook normal diet,and mice in the vitamin D-treated groups were injected with calcitriol（dose of 20,100,500 ng/kg,respectively）three times a week for six weeks,while mice in CON and CKD group were given the same volume of normal saline.After the administration,the Morris water maze experiment was performed on the mice in each group to evaluate the learning and memory ability of the mice,which was divided into two stages: probe trial and hidden-platform trial,spending five days in total.Serum creatinine and urea nitrogen levels were measured using blood samples collected from the orbit,and the pathological changes of the kidney were observed by HE staining and Masson staining to judge whether the animal model was successful.The activity of superoxide dismutase（SOD）were detected to explore the possible mechanism.ResultsAs the experiment progressing,the weight of mice in each group gradually increased.From the end of the fourth week,the weight of mice in the CON group was significantly higher than that of the other four groups（P<0.05）,and the difference was statistically significant.Vitamin D treatment had no significant effect on the body weight of the mice.The results of renal function showed that the levels of serum creatinine and urea nitrogen in the CKD group were higher than those in the CON group（P<0.05）,and urea nitrogen level decreased in the LVD group compared with the CKD group.While no significant difference in creatinine values was observed among the intervention group and the CKD group.The kidneys of the mice in the CON group were generally ruddy in color and full in shape,while in the CKD group the kidneys were small in size and pale in color.HE staining and Masson staining showed that the glomerular structure of mice in the CON group was normal,while the CKD group showed pathological changes such as glomerular atrophy,casts,and interstitial fibrosis.In the probe trial testing,compared with the CON group,the escape latency of the mice in the CKD group was significantly longer（P<0.05）,while the escape latency of the MVD and HVD groups was shorter than that in the CKD group（P<0.05）.In the hidden-platform trial,time and travel distance spent in the original platform quadrant of mice in the CKD group were shorter than those in the CON group（P<0.05）,while the time and distance in the MVD and HVD groups increased compared with those in the CKD group（P<0.05）.The activity of serum SOD was decreased in the CKD group compared with the CON group（P<0.05）,and was increased in the LVD and MVD groups compared with the CKD group（P<0.05）.ConclusionThe cognitive function of chronic kidney disease mice induced by feeding with adenine diet descends,and vitamin D can significantly improve the cognition of CKD mice.Its effect may be related to the inhibition of oxidative stress.