β-Amyloid (1-42)-induced learning and memory deficits in mice: Involvement of oxidative burdens in the hippocampus and cerebral cortex

Jin Hyeong Jhoo, Hyoung Chun Kim, Toshitaka Nabeshima, Kiyofumi Yamada, Eun Joo Shin, Wang Kee Jhoo, Wookyung Kim, Kee Seok Kang, Sangmee Ahn Jo, Jong Inn Woo

Research output: Contribution to journalArticle

127 Citations (Scopus)

Abstract

We have demonstrated that oxidative stress is involved, at least in part, in β-amyloid protein (Aβ)-induced neurotoxicity in vivo [Eur. J. Neurosci. 1999;11:83-90; Neuroscience 2003;119:399-419]. However, mechanistic links between oxidative stress and memory loss in response to Aβ remain elusive. In the present study, we examined whether oxidative stress contributes to the memory deficits induced by intracerebroventricular injection of Aβ (1-42) in mice. Aβ (1-42)-induced memory impairments were observed, as measured by the water maze and passive avoidance tests, although these impairments were not found in Aβ (40-1)-treated mice. Treatment with antioxidant α-tocopherol significantly prevented memory impairment induced by Aβ (1-42). Increased activities of the cytosolic Cu,Zn-superoxide dismutase (Cu,Zn-SOD) and mitochondrial Mn-superoxide dismutase (Mn-SOD) were observed in the hippocampus and cerebral cortex of Aβ (1-42)-treated animals, as compared with Aβ (40-1)-treated mice. The induction of Cu,Zn-SOD was more pronounced than that of Mn-SOD after Aβ (1-42) insult. However, the concomitant induction of glutathione peroxidase (GPX) in response to significant increases in SOD activity was not seen in animals treated with Aβ (1-42). Furthermore, glutathione reductase (GRX) activity was only increased at 2 h after Aβ (1-42) injection. Production of malondialdehyde (lipid peroxidation) and protein carbonyl (protein oxidation) remained elevated at 10 days post-Aβ (1-42), but the antioxidant α-tocopherol significantly prevented these oxidative stresses. Therefore, our results suggest that the oxidative stress contributes to the Aβ (1-42)-induced learning and memory deficits in mice.

Original languageEnglish
Pages (from-to)185-196
Number of pages12
JournalBehavioural Brain Research
Volume155
Issue number2
DOIs
Publication statusPublished - 06-12-2004
Externally publishedYes

Fingerprint

Memory Disorders
Amyloid
Cerebral Cortex
Hippocampus
Oxidative Stress
Learning
Tocopherols
Superoxide Dismutase
Antioxidants
Serum Amyloid A Protein
Injections
Glutathione Reductase
Neurosciences
Glutathione Peroxidase
Malondialdehyde
Lipid Peroxidation
Proteins
Water
Superoxide Dismutase-1

All Science Journal Classification (ASJC) codes

  • Behavioral Neuroscience

Cite this

Jhoo, Jin Hyeong ; Kim, Hyoung Chun ; Nabeshima, Toshitaka ; Yamada, Kiyofumi ; Shin, Eun Joo ; Jhoo, Wang Kee ; Kim, Wookyung ; Kang, Kee Seok ; Jo, Sangmee Ahn ; Woo, Jong Inn. / β-Amyloid (1-42)-induced learning and memory deficits in mice : Involvement of oxidative burdens in the hippocampus and cerebral cortex. In: Behavioural Brain Research. 2004 ; Vol. 155, No. 2. pp. 185-196.
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β-Amyloid (1-42)-induced learning and memory deficits in mice : Involvement of oxidative burdens in the hippocampus and cerebral cortex. / Jhoo, Jin Hyeong; Kim, Hyoung Chun; Nabeshima, Toshitaka; Yamada, Kiyofumi; Shin, Eun Joo; Jhoo, Wang Kee; Kim, Wookyung; Kang, Kee Seok; Jo, Sangmee Ahn; Woo, Jong Inn.

In: Behavioural Brain Research, Vol. 155, No. 2, 06.12.2004, p. 185-196.

Research output: Contribution to journalArticle

TY - JOUR

T1 - β-Amyloid (1-42)-induced learning and memory deficits in mice

T2 - Involvement of oxidative burdens in the hippocampus and cerebral cortex

AU - Jhoo, Jin Hyeong

AU - Kim, Hyoung Chun

AU - Nabeshima, Toshitaka

AU - Yamada, Kiyofumi

AU - Shin, Eun Joo

AU - Jhoo, Wang Kee

AU - Kim, Wookyung

AU - Kang, Kee Seok

AU - Jo, Sangmee Ahn

AU - Woo, Jong Inn

PY - 2004/12/6

Y1 - 2004/12/6

N2 - We have demonstrated that oxidative stress is involved, at least in part, in β-amyloid protein (Aβ)-induced neurotoxicity in vivo [Eur. J. Neurosci. 1999;11:83-90; Neuroscience 2003;119:399-419]. However, mechanistic links between oxidative stress and memory loss in response to Aβ remain elusive. In the present study, we examined whether oxidative stress contributes to the memory deficits induced by intracerebroventricular injection of Aβ (1-42) in mice. Aβ (1-42)-induced memory impairments were observed, as measured by the water maze and passive avoidance tests, although these impairments were not found in Aβ (40-1)-treated mice. Treatment with antioxidant α-tocopherol significantly prevented memory impairment induced by Aβ (1-42). Increased activities of the cytosolic Cu,Zn-superoxide dismutase (Cu,Zn-SOD) and mitochondrial Mn-superoxide dismutase (Mn-SOD) were observed in the hippocampus and cerebral cortex of Aβ (1-42)-treated animals, as compared with Aβ (40-1)-treated mice. The induction of Cu,Zn-SOD was more pronounced than that of Mn-SOD after Aβ (1-42) insult. However, the concomitant induction of glutathione peroxidase (GPX) in response to significant increases in SOD activity was not seen in animals treated with Aβ (1-42). Furthermore, glutathione reductase (GRX) activity was only increased at 2 h after Aβ (1-42) injection. Production of malondialdehyde (lipid peroxidation) and protein carbonyl (protein oxidation) remained elevated at 10 days post-Aβ (1-42), but the antioxidant α-tocopherol significantly prevented these oxidative stresses. Therefore, our results suggest that the oxidative stress contributes to the Aβ (1-42)-induced learning and memory deficits in mice.

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