Cognition impairment in the klotho gene mutant mice and oxidative stress

Taku Nagai, Kiyofumi Yamada, Hyoung Chun Kim, Yukihiro Noda, Yo Ichi Nabeshima, Toshitaka Nabeshima

Research output: Contribution to journalShort survey

4 Citations (Scopus)

Abstract

Klotho is a recently identified gene that is a very different type from those involved in previously described premature-aging syndromes and cell senescence. Although a high level of expression of the klotho gene was detected in the kidney and brain, little is known about the function of the klotho gene in the brain. Here we investigated the changes in mnemonic function accompanying aging in klotho mutant mice. Cognitive function measured by novel-object recognition and conditioned-fear tests in klotho mutant mice was normal at the age of 6 weeks, but markedly impaired at the age of 7 weeks. Lipid peroxide (malondialdehyde) and DNA peroxide (8-hydroxy-2′ -deoxyguanosine) levels in the hippocampus of klotho mutant mice increased at the age of 5 weeks, 2 weeks prior to the development of cognition deficits. Pro-death Bax increased, while anti-death Bcl-2 and Bcl-XL decreased, and apoptotic TUNEL-positive cells were detected in the hippocampus of klotho mutant mice at the age of 7 weeks. A potent antioxidant α-tocopherol prevented the cognition impairment and lipid peroxide accumulation, and decreased the number of apoptotic cells in klotho mutant mice. These results suggest that oxidative stress has a crucial role in the aging-associated cognition impairment in klotho mutant mice. Klotho protein may be involved in the regulation of antioxidative defense.

Original languageEnglish
Pages (from-to)211-217
Number of pages7
JournalJapanese Journal of Neuropsychopharmacology
Volume23
Issue number5
Publication statusPublished - 01-10-2003
Externally publishedYes

Fingerprint

Cognition
Oxidative Stress
Genes
Lipid Peroxides
Hippocampus
Premature Aging
Tocopherols
Cell Aging
In Situ Nick-End Labeling
Brain
Malondialdehyde
Fear
Cell Count
Antioxidants
Kidney
Gene Expression

All Science Journal Classification (ASJC) codes

  • Clinical Psychology
  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)

Cite this

Nagai, T., Yamada, K., Kim, H. C., Noda, Y., Nabeshima, Y. I., & Nabeshima, T. (2003). Cognition impairment in the klotho gene mutant mice and oxidative stress. Japanese Journal of Neuropsychopharmacology, 23(5), 211-217.
Nagai, Taku ; Yamada, Kiyofumi ; Kim, Hyoung Chun ; Noda, Yukihiro ; Nabeshima, Yo Ichi ; Nabeshima, Toshitaka. / Cognition impairment in the klotho gene mutant mice and oxidative stress. In: Japanese Journal of Neuropsychopharmacology. 2003 ; Vol. 23, No. 5. pp. 211-217.
@article{0945e1de0dd24cc9987946f172effb97,
title = "Cognition impairment in the klotho gene mutant mice and oxidative stress",
abstract = "Klotho is a recently identified gene that is a very different type from those involved in previously described premature-aging syndromes and cell senescence. Although a high level of expression of the klotho gene was detected in the kidney and brain, little is known about the function of the klotho gene in the brain. Here we investigated the changes in mnemonic function accompanying aging in klotho mutant mice. Cognitive function measured by novel-object recognition and conditioned-fear tests in klotho mutant mice was normal at the age of 6 weeks, but markedly impaired at the age of 7 weeks. Lipid peroxide (malondialdehyde) and DNA peroxide (8-hydroxy-2′ -deoxyguanosine) levels in the hippocampus of klotho mutant mice increased at the age of 5 weeks, 2 weeks prior to the development of cognition deficits. Pro-death Bax increased, while anti-death Bcl-2 and Bcl-XL decreased, and apoptotic TUNEL-positive cells were detected in the hippocampus of klotho mutant mice at the age of 7 weeks. A potent antioxidant α-tocopherol prevented the cognition impairment and lipid peroxide accumulation, and decreased the number of apoptotic cells in klotho mutant mice. These results suggest that oxidative stress has a crucial role in the aging-associated cognition impairment in klotho mutant mice. Klotho protein may be involved in the regulation of antioxidative defense.",
author = "Taku Nagai and Kiyofumi Yamada and Kim, {Hyoung Chun} and Yukihiro Noda and Nabeshima, {Yo Ichi} and Toshitaka Nabeshima",
year = "2003",
month = "10",
day = "1",
language = "English",
volume = "23",
pages = "211--217",
journal = "Japanese Journal of Psychopharmacology",
issn = "1343-4144",
publisher = "Japanese Society of Neuropsychopharmacology",
number = "5",

}

Nagai, T, Yamada, K, Kim, HC, Noda, Y, Nabeshima, YI & Nabeshima, T 2003, 'Cognition impairment in the klotho gene mutant mice and oxidative stress', Japanese Journal of Neuropsychopharmacology, vol. 23, no. 5, pp. 211-217.

Cognition impairment in the klotho gene mutant mice and oxidative stress. / Nagai, Taku; Yamada, Kiyofumi; Kim, Hyoung Chun; Noda, Yukihiro; Nabeshima, Yo Ichi; Nabeshima, Toshitaka.

In: Japanese Journal of Neuropsychopharmacology, Vol. 23, No. 5, 01.10.2003, p. 211-217.

Research output: Contribution to journalShort survey

TY - JOUR

T1 - Cognition impairment in the klotho gene mutant mice and oxidative stress

AU - Nagai, Taku

AU - Yamada, Kiyofumi

AU - Kim, Hyoung Chun

AU - Noda, Yukihiro

AU - Nabeshima, Yo Ichi

AU - Nabeshima, Toshitaka

PY - 2003/10/1

Y1 - 2003/10/1

N2 - Klotho is a recently identified gene that is a very different type from those involved in previously described premature-aging syndromes and cell senescence. Although a high level of expression of the klotho gene was detected in the kidney and brain, little is known about the function of the klotho gene in the brain. Here we investigated the changes in mnemonic function accompanying aging in klotho mutant mice. Cognitive function measured by novel-object recognition and conditioned-fear tests in klotho mutant mice was normal at the age of 6 weeks, but markedly impaired at the age of 7 weeks. Lipid peroxide (malondialdehyde) and DNA peroxide (8-hydroxy-2′ -deoxyguanosine) levels in the hippocampus of klotho mutant mice increased at the age of 5 weeks, 2 weeks prior to the development of cognition deficits. Pro-death Bax increased, while anti-death Bcl-2 and Bcl-XL decreased, and apoptotic TUNEL-positive cells were detected in the hippocampus of klotho mutant mice at the age of 7 weeks. A potent antioxidant α-tocopherol prevented the cognition impairment and lipid peroxide accumulation, and decreased the number of apoptotic cells in klotho mutant mice. These results suggest that oxidative stress has a crucial role in the aging-associated cognition impairment in klotho mutant mice. Klotho protein may be involved in the regulation of antioxidative defense.

AB - Klotho is a recently identified gene that is a very different type from those involved in previously described premature-aging syndromes and cell senescence. Although a high level of expression of the klotho gene was detected in the kidney and brain, little is known about the function of the klotho gene in the brain. Here we investigated the changes in mnemonic function accompanying aging in klotho mutant mice. Cognitive function measured by novel-object recognition and conditioned-fear tests in klotho mutant mice was normal at the age of 6 weeks, but markedly impaired at the age of 7 weeks. Lipid peroxide (malondialdehyde) and DNA peroxide (8-hydroxy-2′ -deoxyguanosine) levels in the hippocampus of klotho mutant mice increased at the age of 5 weeks, 2 weeks prior to the development of cognition deficits. Pro-death Bax increased, while anti-death Bcl-2 and Bcl-XL decreased, and apoptotic TUNEL-positive cells were detected in the hippocampus of klotho mutant mice at the age of 7 weeks. A potent antioxidant α-tocopherol prevented the cognition impairment and lipid peroxide accumulation, and decreased the number of apoptotic cells in klotho mutant mice. These results suggest that oxidative stress has a crucial role in the aging-associated cognition impairment in klotho mutant mice. Klotho protein may be involved in the regulation of antioxidative defense.

UR - http://www.scopus.com/inward/record.url?scp=0242626707&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0242626707&partnerID=8YFLogxK

M3 - Short survey

VL - 23

SP - 211

EP - 217

JO - Japanese Journal of Psychopharmacology

JF - Japanese Journal of Psychopharmacology

SN - 1343-4144

IS - 5

ER -