Improvement in spatial memory dysfunction by telmisartan through reduction of brain angiotensin II and oxidative stress in experimental uremic mice

Naoki Haruyama, Kiichiro Fujisaki, Mayumi Yamato, Masahiro Eriguchi, Hideko Noguchi, Kumiko Torisu, Kazuhiko Tsuruya, Takanari Kitazono

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Abstract

Aims We previously reported that chronic uremia induces spatial working memory dysfunction in mice, and that it is attributed to cerebral oxidative stress. The source of oxidative stress was considered to be uremic toxins, but this remains unclear. In the present study, we examined whether the brain renin-angiotensin system was activated in the CKD mouse model, and whether it contributed to cognitive impairment. Main methods CKD was induced in 8-week-old male mice by 5/6 nephrectomy. Mice were divided into four groups: control mice administered tap water (Cont-V), control mice treated with 0.5 mg/kg/day telmisartan, an angiotensin II (AII) receptor blocker, for 8 weeks (Cont-T), CKD mice administered tap water (CKD-V), and CKD mice treated with 0.5 mg/kg/day telmisartan for 8 weeks (CKD-T). After the treatment period, a radial arm water maze (RAWM) test was performed, and angiotensin II (AII) concentrations and markers of oxidative stress were measured in the brains of mice. Key findings Errors in the RAWM test were more frequent in the CKD-V group than in the Cont-V group. In addition, errors in the CKD-T group were comparable to control mice. Tissue brain AII concentrations were greater in the CKD-V group compared with the other groups. Oxidative DNA damage and lipid peroxidation in the brain were also greater in the CKD-V group compared with the other groups. Significance Our results suggest that brain AII levels were exaggerated in CKD mice, and that this contributes to cognitive impairment through oxidative stress.

Original languageEnglish
Pages (from-to)55-59
Number of pages5
JournalLife Sciences
Volume113
Issue number1-2
DOIs
Publication statusPublished - Sep 15 2014

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All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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