title: Improvement in spatial memory dysfunction by telmisartan through reduction of brain angiotensin II and oxidative stress in experimental uremic mice.
abstract: OBJECTIVE
  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.
  
  
  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 0.5mg/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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Our results suggest that brain AII levels were exaggerated in CKD mice, and that this contributes to cognitive impairment through oxidative stress.
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Haruyama
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Kiichiro
authors.initials: K
authors.lastname: Fujisaki
authors.affiliation: Department of REDOX Medicinal Science, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Yamato
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Eriguchi
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Hideko
authors.initials: H
authors.lastname: Noguchi
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Kumiko
authors.initials: K
authors.lastname: Torisu
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Department of Integrated Therapy for Chronic Kidney Disease, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. Electronic address: tsuruya@intmed2.med.kyushu-u.ac.jp.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Tsuruya
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Takanari
authors.initials: T
authors.lastname: Kitazono
mesh_terms: D000804:Angiotensin II / Q000378:metabolism*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000737:chemistry; D000818:Animals; D001562:Benzimidazoles / Q000737:chemistry*; D001565:Benzoates / Q000737:chemistry*; D001921:Brain / Q000378:metabolism; D003072:Cognition Disorders / Q000188:drug therapy; D004249:DNA Damage; D015227:Lipid Peroxidation; D008297:Male; D018782:Maze Learning; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D009392:Nephrectomy; D018384:Oxidative Stress; D015203:Reproducibility of Results; D013037:Spatial Behavior / Q000187:drug effects* / Q000502:physiology; D000077333:Telmisartan; D014511:Uremia / Q000503:physiopathology*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001565:Benzoates; D000804:Angiotensin II; D000077333:Telmisartan
keywords: 2-thiobarbituric acid (PubChem CID: 2723628); 8-oxo-hydroxydeoxyguanosine (PubChem CID: 73318); Angiotensin II (PubChem CID: 172198); Brain angiotensin II; Chronic kidney disease; Cognitive impairment; Florisil (PubChem CID: 61680); Malondialdehyde (PubChem CID: 10964); Oxidative stress; Telmisartan; Telmisartan (PubChem CID: 65999)