Zhian Lv1, Jie Gao1, Li Wang1, Zhao Chen1, Haozheng Yuan2, Xiaoqin Ma1, Jiamei Lu1, Jianrui Lv2, Xili Wu3, Lei Zhang4, Linting Wei1, Rongliang Xue2, Rongguo Fu5, Liqun Ma6. 1. Department of Nephrology, Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, 710004, Shaanxi Province, People's Republic of China. 2. Department of Anesthesia, Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, 710004, Shaanxi Province, People's Republic of China. 3. Department of Integrated Chinese Traditional and Western Medicine, Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, 710004, Shaanxi Province, People's Republic of China. 4. Medical Laboratory, Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, 710004, Shaanxi Province, People's Republic of China. 5. Department of Nephrology, Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, 710004, Shaanxi Province, People's Republic of China. pipifu@126.com. 6. Department of Nephrology, Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, 710004, Shaanxi Province, People's Republic of China. maliqun-doctor@tom.com.
Abstract
PURPOSE: Hippocampus plays an important role in spatial learning and memory. Ghrelin, a brain-gut peptide, participates in the mnestic functions of hippocampus through its receptor growth hormone secretagogue receptor (GHS-R) distributed in hippocampus. This study was to investigate whether there was a correlation between the changes of ghrelin system in hippocampus and the spatial cognitive impairment caused by chronic renal failure (CRF). METHODS: Sprague-Dawley rats (male, 180 ± 10 g, 7-8 weeks old) were randomly classified into CRF group and control group (n = 18 per group). The CRF model was constructed by 5/6 nephrectomy and the controls treated with sham operation. By the 8th week after the surgery, the spatial cognitive function of rats was assessed by Morris water-maze test (MWM), the protein expression of ghrelin and GHS-R in the hippocampus by immunohistochemistry, and the mRNA expression by real-time PCR. Statistical analysis was performed using ANOVA, Student-Newman-Keuls-q test and Pearson correlation analysis, and P < 0.05 was considered significant. RESULTS: Compared with the controls, the time spent in "platform" quadrant (TSPQ) of rats with CRF was decreased, but the escape latency (EL) was increased significantly in MWM, and meanwhile the protein and mRNA expression of ghrelin and GHS-R in hippocampus was also increased significantly (P < 0.05 or P < 0.01). Correlation analysis suggested that the TSPQ was negatively but the EL was positively correlated with the mRNA expression of ghrelin and GHS-R (P < 0.01). CONCLUSION: The CRF-caused changes of ghrelin system in hippocampus might be correlated with the CRF-caused cognitive function impairment.
PURPOSE: Hippocampus plays an important role in spatial learning and memory. Ghrelin, a brain-gut peptide, participates in the mnestic functions of hippocampus through its receptor growth hormone secretagogue receptor (GHS-R) distributed in hippocampus. This study was to investigate whether there was a correlation between the changes of ghrelin system in hippocampus and the spatial cognitive impairment caused by chronic renal failure (CRF). METHODS:Sprague-Dawley rats (male, 180 ± 10 g, 7-8 weeks old) were randomly classified into CRF group and control group (n = 18 per group). The CRF model was constructed by 5/6 nephrectomy and the controls treated with sham operation. By the 8th week after the surgery, the spatial cognitive function of rats was assessed by Morris water-maze test (MWM), the protein expression of ghrelin and GHS-R in the hippocampus by immunohistochemistry, and the mRNA expression by real-time PCR. Statistical analysis was performed using ANOVA, Student-Newman-Keuls-q test and Pearson correlation analysis, and P < 0.05 was considered significant. RESULTS: Compared with the controls, the time spent in "platform" quadrant (TSPQ) of rats with CRF was decreased, but the escape latency (EL) was increased significantly in MWM, and meanwhile the protein and mRNA expression of ghrelin and GHS-R in hippocampus was also increased significantly (P < 0.05 or P < 0.01). Correlation analysis suggested that the TSPQ was negatively but the EL was positively correlated with the mRNA expression of ghrelin and GHS-R (P < 0.01). CONCLUSION: The CRF-caused changes of ghrelin system in hippocampus might be correlated with the CRF-caused cognitive function impairment.
Entities:
Keywords:
Chronic renal failure; Ghrelin; Hippocampus; Spatial cognitive function impairment