Impairment of Learning and Memory in Rats Caused by Oxidative Stress and Aging, and Changes in Antioxidative Defense Systems

Fukui, Koji; Onodera, Kônoshin; Senoo, Tadashi; Suzuki, Sadao; Urano, Shiro

doi:10.1111/j.1749-6632.2001.tb05646.x

Cited by 246 publications

(121 citation statements)

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“…Furthermore, deficiency of vitamin E accelerates oxidative damage in the brain. Vitamin E-deficient rats have lower activity of antioxidant enzymes and increased lipid peroxidation in the brain (10,11). It is possible that enhancement of oxidative damage of vitamin E-deficient models affects autophagy.…”

Section: Increased Expression Of Map-lc3 In the Cerebral Cortex And Hmentioning

confidence: 99%

“…In a previous study, we demonstrated that vitamin E-deficient rats exhibited cognitive dysfunction in several maze tasks (10,11). We have been studying the mechanisms of cognitive dysfunction in this animal model, and have found evidence of apoptosis and b-amyloid-like proteins in the hipocampal CA1 region (12), indicating that cognitive dysfunction in vitamin E-deficient animals may be connected with injury to hippocampal neurons.…”

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confidence: 99%

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Vitamin E Deficiency Induces Axonal Degeneration in Mouse Hippocampal Neurons

Fukui

Kawakami

Honjo

et al. 2012

J Nutr Sci Vitaminol

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SummarySeveral lines of evidence demonstrate the relationship between vitamin E deficiency and cognitive dysfunction in rodent models, but little is known about the underlying mechanisms. In this study, we found axonal injury in the hippocampal CA1 region of vitamin E-deficient and normal old mice using immunohistochemical assay. The number of cells in the hippocampal CA1 region of vitamin E-deficient mice and normal old mice was significantly lower than in normal young mice. It is well known that collapsin response mediator protein (CRMP)-2 plays a crucial role in the maintenance of axonal conditions. The expressions of CRMP-2 in the cerebral cortex and hippocampus of vitamin E-deficient mice were significantly lower than both the regions of normal ones. In normal old mice, the expression of CRMP-2 in the cerebral cortex was significantly lower than in the normal ones. In addition, the appearance of microtubule-associated protein (MAP)-light chain 3 (LC3), a major index of autophagy, was higher in the cerebral cortex and hippocampus of vitamin E-deficient mice than in normal young and old mice. These results indicate that axonal degeneration is induced in living tissues, but not cultured cells, and that changes in CRMP-2 and MAP-LC3 may underlie vitamin E-deficiency-related axonal degeneration.

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Section: Increased Expression Of Map-lc3 In the Cerebral Cortex And Hmentioning

confidence: 99%

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confidence: 99%

Vitamin E Deficiency Induces Axonal Degeneration in Mouse Hippocampal Neurons

Fukui

Kawakami

Honjo

et al. 2012

J Nutr Sci Vitaminol

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“…In another study, it was shown that free O 2 radicals increased in diabetic rat brains, and these increased O 2 -free radicals were decreased using an ET-1 antagonist [57]. Long-term oxidative damage leads to morphological damage and memory disorders in many parts of the brain [58,59], and one previous study showed that diabetes-induced hippocampal neuron damage was prevented by antioxidant therapy [60]. As an indicator of lipid peroxidation and oxidative stress, MDA levels were found to be quite high in the diabetic rats.…”

Section: Discussionmentioning

confidence: 99%

Does Bosentan Protect Diabetic Brain Alterations in Rats? The Role of Endothelin‐1 in the Diabetic Brain

Demir

Çadırcı

Akpınar

et al. 2014

Basic Clin Pharma Tox

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Diabetes mellitus (DM) is a major problem all over the world, affecting more people in recent years. Individuals with diabetes are more prone to disease than non-diabetics, especially vascular complications. The aim of this study was to examine the roles of the endothelin (ET)-1 in brain damage formed in a streptozocin (STZ)-induced diabetes model, and the effect of bosentan, which is the non-specific ET1 receptor blocker in the prevention of the diabetes-induced brain damage. To examine the effects of bosentan (50 mg/kg and 100 mg/kg) in this study, the rats were given the drug for 3 months. The rats were divided into four groups: the sham group (n = 10), the diabetic control group (n = 10), the group of diabetic rats given bosentan 50 mg/ kg (n = 10) and the group of diabetic rats given bosentan 100 mg/kg (n = 10). Diabetes was induced in the rats by STZ (60 mg/kg i.p.). On day 91, all rats were killed. Brain tissues of the rats were measured by molecular, biochemical and histopathological methods. Antioxidant levels in the therapy groups were observed as quite near to the values in the healthy group. In this study, while the brain eNOS levels in the diabetic groups decreased, the ET1 and iNOS levels were found to be increased. However, in the diabetes group, hippocampus and cerebellum, pericellular oedema and a number of neuronal cytoretraction were increased in neuropiles, whereas these results were decreased in the therapy group. Based on all of these results, ET1 will not be ignored in diabetes-induced cerebral complications.Diabetes mellitus (DM) is a severe disease which eventually results in death. During diabetes mellitus, tissues cannot uptake glucose and very severe complications such as nephropathy, retinopathy, neuropathy and peripheral vascular complications occur [1]. Many new mechanisms have been suggested during the formation and progress of these complications. There are studies in many areas, from inflammation to cellular membrane disorders, of the mechanisms of diabetesinduced complications [1][2][3]. There are also many studies on the receptors which are responsible for the formation of diabetes and diabetes-induced complications in relation to our topic: angiotensin receptors, urotensin receptors, glucagon-like peptide 1 receptors and peroxisome proliferator-activated receptora [4,5].Previous studies have shown the importance of angiotensin in diabetes-induced liver damage [6,7], and there are many recent studies showing that endothelin-1 receptors play important roles in diabetes. One study showed that cell proliferation and, at the same time, ET1 production increased in type 2 diabetes [8,9]. Diabetes-related, clinical and experimental studies showed that ET1 plasma levels increased [10,11]. A study by Mastumoto et al. showed that the expression of both ET1 and the receptors increased in the streptozotocin (STZ)-induced diabetes model [12]. In another study, giving endothelin-1 to individuals with insulin resistance reduced endothelin-1-induced vasodilatation [13]. ET1 levels w...

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“…Our previous study showed that young rats subjected to hyperoxia as oxidative stress reveal marked deficits in learning and memory functions, and that the delayed-type apoptosis of pyramidal cells is induced after oxidative stress [8]. These abnormalities are also observed in both old rats and vitamin E-deficient young rats not subjected to oxidative stress [9].…”

Section: Introductionmentioning

confidence: 90%

Increased F2-Isoprostane Levels in the Rat Brain and Plasma Caused by Oxidative Stress and Aging, and Inhibitory Effect of Vitamin E

Nishio

Miyadera

Sakai

et al. 2006

J. Clin. Biochem. Nutr.

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Summary To determine whether lipid peroxidation induced by reactive oxygen species (ROS) is a causal factor of neurodegeneration during brain aging, we investigated whether F2-isoprostanes, non-cyclooxygenase-derived prostanoids, are formed in the rat brain and plasma by hyperoxia as oxidative stress, and whether their formation is associated with vitamin E status in vivo in association with changes that occur during brain aging. Young rats subjected to hyperoxia for 48 h revealed a marked increase in the levels of F2-isoprostanes in the brain, but not in plasma. A similar increase in F2-isoprostane level was observed in aged rats kept in normal atmosphere. Vitamin E supplementation to young rats markedly inhibited F2-isoprostane formation even after hyperoxia. In contrast, vitamin E-deficient young rats kept in normal atmosphere showed a significant increase in F2-isoprostane level in the brain. These findings indicate that F2-isoprostane formation in the brain has important implications in the etiology of neurodegenerative diseases including Alzheimer's disease during aging, and that the analysis of F2-isoprostane level in plasma does not always reflect neuronal damage cause by oxidative stress. Vitamin E may protect neuronal damage in the brain caused by oxidative stress experienced for a long period during aging.

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Impairment of Learning and Memory in Rats Caused by Oxidative Stress and Aging, and Changes in Antioxidative Defense Systems

Cited by 246 publications

References 8 publications

Vitamin E Deficiency Induces Axonal Degeneration in Mouse Hippocampal Neurons

Vitamin E Deficiency Induces Axonal Degeneration in Mouse Hippocampal Neurons

Does Bosentan Protect Diabetic Brain Alterations in Rats? The Role of Endothelin‐1 in the Diabetic Brain

Increased F2-Isoprostane Levels in the Rat Brain and Plasma Caused by Oxidative Stress and Aging, and Inhibitory Effect of Vitamin E

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