Cerebral oxidative stress induces spatial working memory dysfunction in uremic mice: Neuroprotective effect of tempol

Kiichiro Fujisaki, Kazuhiko Tsuruya, Mayumi Yamato, Jiro Toyonaga, Hideko Noguchi, Toshiaki Nakano, Masatomo Taniguchi, Masanori Tokumoto, Hideki Hirakata, Takanari Kitazono

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

BackgroundChronic kidney disease (CKD) is frequently associated with uremic encephalopathy and cognitive impairment. Recent studies have demonstrated that cerebral oxidative stress contributes to cognitive dysfunction. Although oxidative stress has been reported to increase in the uremic rat brain, the relationship between increased oxidative stress and cognitive impairment in uremia is unclear. In the present study, the effects of tempol (TMP), an antioxidant drug, were investigated in uremic mice.MethodsCKD was induced in male C57BL/6 mice (n = 8) by left nephrectomy and 2/3 electrocoagulation of the right renal cortex. Working memory performance was tested by the radial arm water maze test. We have prepared two protocols ('time course study' and 'treatment study'). First, we examined the working memory test and histological examination of mouse brains after 4 and 8 weeks. Next, we investigated the effect of TMP (3 mM) against uremia-induced neurodegeneration and oxidative stress in the mouse brain.ResultsEight weeks after CKD induction, vehicle-treated mice made significantly more errors than sham-operated control mice, while TMP improved working memory performance in CKD mice. CKD was associated with accumulation of 8-hydroxy-2′-deoxyguanosine in the hippocampal neuronal cells, but not in TMP-treated CKD mice. Increased numbers of pyknotic neuronal cells were observed in the hippocampus of CKD mice at 8 weeks, but pyknotic neuronal cell numbers were decreased under the influence of TMP in uremic mice.ConclusionsThe present study provided evidence that uremia is associated with spatial working memory dysfunction in mice and that treatment with TMP protects against cerebral oxidative stress and improves cognitive dysfunction in uremic mice, suggesting their potential usefulness for the treatment of cognitive dysfunction in uremia.

Original languageEnglish (US)
Pages (from-to)529-538
Number of pages10
JournalNephrology Dialysis Transplantation
Volume29
Issue number3
DOIs
StatePublished - 2014

Fingerprint

Neuroprotective Agents
Short-Term Memory
Oxidative Stress
Uremia
Brain
Spatial Memory
tempol
Electrocoagulation
Kidney Diseases
Brain Diseases
Nephrectomy
Inbred C57BL Mouse
Hippocampus
Therapeutics
Cell Count
Antioxidants
Cognitive Dysfunction
Kidney

Keywords

  • Chronic kidney disease
  • Cognitive dysfunction
  • Oxidative stress
  • Uremia

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

Cite this

Cerebral oxidative stress induces spatial working memory dysfunction in uremic mice : Neuroprotective effect of tempol. / Fujisaki, Kiichiro; Tsuruya, Kazuhiko; Yamato, Mayumi; Toyonaga, Jiro; Noguchi, Hideko; Nakano, Toshiaki; Taniguchi, Masatomo; Tokumoto, Masanori; Hirakata, Hideki; Kitazono, Takanari.

In: Nephrology Dialysis Transplantation, Vol. 29, No. 3, 2014, p. 529-538.

Research output: Contribution to journalArticle

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', Nephrology Dialysis Transplantation, vol. 29, no. 3, pp. 529-538. https://doi.org/10.1093/ndt/gft327
Fujisaki, Kiichiro ; Tsuruya, Kazuhiko ; Yamato, Mayumi ; Toyonaga, Jiro ; Noguchi, Hideko ; Nakano, Toshiaki ; Taniguchi, Masatomo ; Tokumoto, Masanori ; Hirakata, Hideki ; Kitazono, Takanari. / Cerebral oxidative stress induces spatial working memory dysfunction in uremic mice : Neuroprotective effect of tempol. In: Nephrology Dialysis Transplantation. 2014 ; Vol. 29, No. 3. pp. 529-538.
@article{fde39094bd3a4f119ad63958f689bd97,
title = "Cerebral oxidative stress induces spatial working memory dysfunction in uremic mice: Neuroprotective effect of tempol",
abstract = "BackgroundChronic kidney disease (CKD) is frequently associated with uremic encephalopathy and cognitive impairment. Recent studies have demonstrated that cerebral oxidative stress contributes to cognitive dysfunction. Although oxidative stress has been reported to increase in the uremic rat brain, the relationship between increased oxidative stress and cognitive impairment in uremia is unclear. In the present study, the effects of tempol (TMP), an antioxidant drug, were investigated in uremic mice.MethodsCKD was induced in male C57BL/6 mice (n = 8) by left nephrectomy and 2/3 electrocoagulation of the right renal cortex. Working memory performance was tested by the radial arm water maze test. We have prepared two protocols ('time course study' and 'treatment study'). First, we examined the working memory test and histological examination of mouse brains after 4 and 8 weeks. Next, we investigated the effect of TMP (3 mM) against uremia-induced neurodegeneration and oxidative stress in the mouse brain.ResultsEight weeks after CKD induction, vehicle-treated mice made significantly more errors than sham-operated control mice, while TMP improved working memory performance in CKD mice. CKD was associated with accumulation of 8-hydroxy-2′-deoxyguanosine in the hippocampal neuronal cells, but not in TMP-treated CKD mice. Increased numbers of pyknotic neuronal cells were observed in the hippocampus of CKD mice at 8 weeks, but pyknotic neuronal cell numbers were decreased under the influence of TMP in uremic mice.ConclusionsThe present study provided evidence that uremia is associated with spatial working memory dysfunction in mice and that treatment with TMP protects against cerebral oxidative stress and improves cognitive dysfunction in uremic mice, suggesting their potential usefulness for the treatment of cognitive dysfunction in uremia.",
keywords = "Chronic kidney disease, Cognitive dysfunction, Oxidative stress, Uremia",
author = "Kiichiro Fujisaki and Kazuhiko Tsuruya and Mayumi Yamato and Jiro Toyonaga and Hideko Noguchi and Toshiaki Nakano and Masatomo Taniguchi and Masanori Tokumoto and Hideki Hirakata and Takanari Kitazono",
year = "2014",
doi = "10.1093/ndt/gft327",
language = "English (US)",
volume = "29",
pages = "529--538",
journal = "Nephrology Dialysis Transplantation",
issn = "0931-0509",
publisher = "Oxford University Press",
number = "3",

}

TY - JOUR

T1 - Cerebral oxidative stress induces spatial working memory dysfunction in uremic mice

T2 - Neuroprotective effect of tempol

AU - Fujisaki, Kiichiro

AU - Tsuruya, Kazuhiko

AU - Yamato, Mayumi

AU - Toyonaga, Jiro

AU - Noguchi, Hideko

AU - Nakano, Toshiaki

AU - Taniguchi, Masatomo

AU - Tokumoto, Masanori

AU - Hirakata, Hideki

AU - Kitazono, Takanari

PY - 2014

Y1 - 2014

N2 - BackgroundChronic kidney disease (CKD) is frequently associated with uremic encephalopathy and cognitive impairment. Recent studies have demonstrated that cerebral oxidative stress contributes to cognitive dysfunction. Although oxidative stress has been reported to increase in the uremic rat brain, the relationship between increased oxidative stress and cognitive impairment in uremia is unclear. In the present study, the effects of tempol (TMP), an antioxidant drug, were investigated in uremic mice.MethodsCKD was induced in male C57BL/6 mice (n = 8) by left nephrectomy and 2/3 electrocoagulation of the right renal cortex. Working memory performance was tested by the radial arm water maze test. We have prepared two protocols ('time course study' and 'treatment study'). First, we examined the working memory test and histological examination of mouse brains after 4 and 8 weeks. Next, we investigated the effect of TMP (3 mM) against uremia-induced neurodegeneration and oxidative stress in the mouse brain.ResultsEight weeks after CKD induction, vehicle-treated mice made significantly more errors than sham-operated control mice, while TMP improved working memory performance in CKD mice. CKD was associated with accumulation of 8-hydroxy-2′-deoxyguanosine in the hippocampal neuronal cells, but not in TMP-treated CKD mice. Increased numbers of pyknotic neuronal cells were observed in the hippocampus of CKD mice at 8 weeks, but pyknotic neuronal cell numbers were decreased under the influence of TMP in uremic mice.ConclusionsThe present study provided evidence that uremia is associated with spatial working memory dysfunction in mice and that treatment with TMP protects against cerebral oxidative stress and improves cognitive dysfunction in uremic mice, suggesting their potential usefulness for the treatment of cognitive dysfunction in uremia.

AB - BackgroundChronic kidney disease (CKD) is frequently associated with uremic encephalopathy and cognitive impairment. Recent studies have demonstrated that cerebral oxidative stress contributes to cognitive dysfunction. Although oxidative stress has been reported to increase in the uremic rat brain, the relationship between increased oxidative stress and cognitive impairment in uremia is unclear. In the present study, the effects of tempol (TMP), an antioxidant drug, were investigated in uremic mice.MethodsCKD was induced in male C57BL/6 mice (n = 8) by left nephrectomy and 2/3 electrocoagulation of the right renal cortex. Working memory performance was tested by the radial arm water maze test. We have prepared two protocols ('time course study' and 'treatment study'). First, we examined the working memory test and histological examination of mouse brains after 4 and 8 weeks. Next, we investigated the effect of TMP (3 mM) against uremia-induced neurodegeneration and oxidative stress in the mouse brain.ResultsEight weeks after CKD induction, vehicle-treated mice made significantly more errors than sham-operated control mice, while TMP improved working memory performance in CKD mice. CKD was associated with accumulation of 8-hydroxy-2′-deoxyguanosine in the hippocampal neuronal cells, but not in TMP-treated CKD mice. Increased numbers of pyknotic neuronal cells were observed in the hippocampus of CKD mice at 8 weeks, but pyknotic neuronal cell numbers were decreased under the influence of TMP in uremic mice.ConclusionsThe present study provided evidence that uremia is associated with spatial working memory dysfunction in mice and that treatment with TMP protects against cerebral oxidative stress and improves cognitive dysfunction in uremic mice, suggesting their potential usefulness for the treatment of cognitive dysfunction in uremia.

KW - Chronic kidney disease

KW - Cognitive dysfunction

KW - Oxidative stress

KW - Uremia

UR - http://www.scopus.com/inward/record.url?scp=84895762758&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84895762758&partnerID=8YFLogxK

U2 - 10.1093/ndt/gft327

DO - 10.1093/ndt/gft327

M3 - Article

C2 - 24030834

AN - SCOPUS:84895762758

VL - 29

SP - 529

EP - 538

JO - Nephrology Dialysis Transplantation

JF - Nephrology Dialysis Transplantation

SN - 0931-0509

IS - 3

ER -