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Published in: International Urology and Nephrology 5/2016

01-05-2016 | Nephrology - Original Paper

Uremia-caused changes of ghrelin system in hippocampus may be associated with impaired cognitive function of hippocampus

Authors: Zhian Lv, Jie Gao, Li Wang, Zhao Chen, Haozheng Yuan, Xiaoqin Ma, Jiamei Lu, Jianrui Lv, Xili Wu, Lei Zhang, Linting Wei, Rongliang Xue, Rongguo Fu, Liqun Ma

Published in: International Urology and Nephrology | Issue 5/2016

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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.
Literature
4.
go back to reference Fujisaki K, Tsuruya K, Yamato M, Toyonaga J, Noguchi H, Nakano T, Taniguchi M, Tokumoto M, Hirakata H, Kitazono T (2014) Cerebral oxidative stress induces spatial working memory dysfunction in uremic mice: neuroprotective effect of tempol. Nephrol Dial Transplant 29(3):529–538. doi:10.1093/ndt/gft327 CrossRefPubMed Fujisaki K, Tsuruya K, Yamato M, Toyonaga J, Noguchi H, Nakano T, Taniguchi M, Tokumoto M, Hirakata H, Kitazono T (2014) Cerebral oxidative stress induces spatial working memory dysfunction in uremic mice: neuroprotective effect of tempol. Nephrol Dial Transplant 29(3):529–538. doi:10.​1093/​ndt/​gft327 CrossRefPubMed
5.
9.
go back to reference Carlini VP, Varas MM, Cragnolini AB, Schioth HB, Scimonelli TN, de Barioglio SR (2004) Differential role of the hippocampus, amygdala, and dorsal raphe nucleus in regulating feeding, memory, and anxiety-like behavioral responses to ghrelin. Biochem Biophys Res Commun 313(3):635–641. doi:10.1016/j.bbrc.2003.11.150 CrossRefPubMed Carlini VP, Varas MM, Cragnolini AB, Schioth HB, Scimonelli TN, de Barioglio SR (2004) Differential role of the hippocampus, amygdala, and dorsal raphe nucleus in regulating feeding, memory, and anxiety-like behavioral responses to ghrelin. Biochem Biophys Res Commun 313(3):635–641. doi:10.​1016/​j.​bbrc.​2003.​11.​150 CrossRefPubMed
12.
go back to reference Swanson LW (2004) Brain maps III: structure of the rat brain: an atlas with printed and electronic templates for data, models, and schematics, 3rd rev. edn. Elsevier, Amsterdam Swanson LW (2004) Brain maps III: structure of the rat brain: an atlas with printed and electronic templates for data, models, and schematics, 3rd rev. edn. Elsevier, Amsterdam
14.
go back to reference Al Banchaabouchi M, D’Hooge R, Marescau B, De Deyn PP (1999) Behavioural deficits during the acute phase of mild renal failure in mice. Metab Brain Dis 14(3):173–187CrossRefPubMed Al Banchaabouchi M, D’Hooge R, Marescau B, De Deyn PP (1999) Behavioural deficits during the acute phase of mild renal failure in mice. Metab Brain Dis 14(3):173–187CrossRefPubMed
15.
go back to reference Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K (1999) Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 402(6762):656–660. doi:10.1038/45230 CrossRefPubMed Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K (1999) Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 402(6762):656–660. doi:10.​1038/​45230 CrossRefPubMed
16.
go back to reference Cowley MA, Smith RG, Diano S, Tschop M, Pronchuk N, Grove KL, Strasburger CJ, Bidlingmaier M, Esterman M, Heiman ML, Garcia-Segura LM, Nillni EA, Mendez P, Low MJ, Sotonyi P, Friedman JM, Liu HY, Pinto S, Colmers WF, Cone RD, Horvath TL (2003) The distribution and mechanism of action of ghrelin in the CNS demonstrates a novel hypothalamic circuit regulating energy homeostasis. Neuron 37(4):649–661. doi:10.1016/S0896-6273(03)00063-1 CrossRefPubMed Cowley MA, Smith RG, Diano S, Tschop M, Pronchuk N, Grove KL, Strasburger CJ, Bidlingmaier M, Esterman M, Heiman ML, Garcia-Segura LM, Nillni EA, Mendez P, Low MJ, Sotonyi P, Friedman JM, Liu HY, Pinto S, Colmers WF, Cone RD, Horvath TL (2003) The distribution and mechanism of action of ghrelin in the CNS demonstrates a novel hypothalamic circuit regulating energy homeostasis. Neuron 37(4):649–661. doi:10.​1016/​S0896-6273(03)00063-1 CrossRefPubMed
17.
go back to reference Braak H, Braak E, Yilmazer D, Bohl J (1996) Functional anatomy of human hippocampal formation and related structures. J Child Neurol 11(4):265–275CrossRefPubMed Braak H, Braak E, Yilmazer D, Bohl J (1996) Functional anatomy of human hippocampal formation and related structures. J Child Neurol 11(4):265–275CrossRefPubMed
18.
go back to reference Mcclelland JL, Mcnaughton BL, Oreilly RC (1995) Why there are complementary learning-systems in the hippocampus and neocortex—insights from the successes and failures of connectionist models of learning and memory. Psychol Rev 102(3):419–457. doi:10.1037/0033-295x.102.3.419 CrossRefPubMed Mcclelland JL, Mcnaughton BL, Oreilly RC (1995) Why there are complementary learning-systems in the hippocampus and neocortex—insights from the successes and failures of connectionist models of learning and memory. Psychol Rev 102(3):419–457. doi:10.​1037/​0033-295x.​102.​3.​419 CrossRefPubMed
20.
go back to reference Lee I, Kesner RP (2004) Encoding versus retrieval of spatial memory: double dissociation between the dentate gyrus and the perforant path inputs into CA3 in the dorsal hippocampus. Hippocampus 14(1):66–76. doi:10.1002/hipo.10167 CrossRefPubMed Lee I, Kesner RP (2004) Encoding versus retrieval of spatial memory: double dissociation between the dentate gyrus and the perforant path inputs into CA3 in the dorsal hippocampus. Hippocampus 14(1):66–76. doi:10.​1002/​hipo.​10167 CrossRefPubMed
21.
23.
go back to reference Diano S, Farr SA, Benoit SC, McNay EC, da Silva I, Horvath B, Gaskin FS, Nonaka N, Jaeger LB, Banks WA, Morley JE, Pinto S, Sherwin RS, Xu L, Yamada KA, Sleeman MW, Tschop MH, Horvath TL (2006) Ghrelin controls hippocampal spine synapse density and memory performance. Nat Neurosci 9(3):381–388. doi:10.1038/Nn1656 CrossRefPubMed Diano S, Farr SA, Benoit SC, McNay EC, da Silva I, Horvath B, Gaskin FS, Nonaka N, Jaeger LB, Banks WA, Morley JE, Pinto S, Sherwin RS, Xu L, Yamada KA, Sleeman MW, Tschop MH, Horvath TL (2006) Ghrelin controls hippocampal spine synapse density and memory performance. Nat Neurosci 9(3):381–388. doi:10.​1038/​Nn1656 CrossRefPubMed
25.
go back to reference Jiang H, Betancourt L, Smith RG (2006) Ghrelin amplifies dopamine signaling by cross talk involving formation of growth hormone secretagogue receptor/dopamine receptor subtype 1 heterodimers. Mol Endocrinol 20(8):1772–1785. doi:10.1210/Me.2005-0084 CrossRefPubMed Jiang H, Betancourt L, Smith RG (2006) Ghrelin amplifies dopamine signaling by cross talk involving formation of growth hormone secretagogue receptor/dopamine receptor subtype 1 heterodimers. Mol Endocrinol 20(8):1772–1785. doi:10.​1210/​Me.​2005-0084 CrossRefPubMed
27.
go back to reference Fujisaki K, Tsuruya K, Yamato M, Toyonaga J, Noguchi H, Nakano T, Taniguchi M, Tokumoto M, Hirakata H, Kitazono T (2014) Cerebral oxidative stress induces spatial working memory dysfunction in uremic mice: neuroprotective effect of tempol. Nephrol Dial Transpl 29(3):529–538. doi:10.1093/ndt/gft327 CrossRef Fujisaki K, Tsuruya K, Yamato M, Toyonaga J, Noguchi H, Nakano T, Taniguchi M, Tokumoto M, Hirakata H, Kitazono T (2014) Cerebral oxidative stress induces spatial working memory dysfunction in uremic mice: neuroprotective effect of tempol. Nephrol Dial Transpl 29(3):529–538. doi:10.​1093/​ndt/​gft327 CrossRef
30.
Metadata
Title
Uremia-caused changes of ghrelin system in hippocampus may be associated with impaired cognitive function of hippocampus
Authors
Zhian Lv
Jie Gao
Li Wang
Zhao Chen
Haozheng Yuan
Xiaoqin Ma
Jiamei Lu
Jianrui Lv
Xili Wu
Lei Zhang
Linting Wei
Rongliang Xue
Rongguo Fu
Liqun Ma
Publication date
01-05-2016
Publisher
Springer Netherlands
Published in
International Urology and Nephrology / Issue 5/2016
Print ISSN: 0301-1623
Electronic ISSN: 1573-2584
DOI
https://doi.org/10.1007/s11255-016-1228-9

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