Cognitive Impairment of Rats Caused by Oxidative Stress and Aging, and Its Prevention by Vitamin E

Abstract

In order to verify whether brain damage caused by chronic oxidative stress induces the impairment of cognitive function, the ability of learning and memory was assessed using the water maze and the eight-arm radial maze tasks. Young rats showed significantly greater learning ability before the stress than the old and vitamin E-deficient rats. At five days after subjection to oxidative stress, the memory function of the young declined toward the level of that in the aged rats maintained under normal condition. This phenomenon is supported by the findings that the delayed-type apoptosis appeared in the CA1 region of the hippocampus of the young at five to seven days after the stress. Vitamin E supplementation to the young accelerated significantly their learning functions before the stress and prevented the deficit of memory caused by the stress. When rats were subjected to stress, thiobarbituric acid-reactive substance (TBARS), lipid hydroperoxides, and protein carbonyls were significantly increased in synaptic plasma membranes. It was found that zeta-potential of the synaptic membrane surface was remarkably decreased. These phenomena were also observed in the aged and vitamin E-deficient rats maintained under normal condition. These results suggest that oxidative damage to the rat synapse in the cerebral cortex and hippocampus during aging may contribute to the deficit of cognitive functions.

Reversal of aging‐associated hippocampal synaptic plasticity deficits by reductants via regulation of thiol redox and NMDA receptor function

“…The fact that acute application of vitamin C and trolox in vitro could not reverse aging-associated impairment of NMDAR-dependent LTP in rat hippocampus in this study suggests that administration of antioxidants, which can reduce ROS generation but not reverse oxidative inactivation of key functional macromolecules directly, has little acute effect on aging-related deficits in synaptic plasticity. In fact, most of the previous studies have indicated that chronic administration of antioxidants for a longer period of time could attenuate aging-related cognitive disorders (Clausen et al;Fukui et al, 2002;Head, 2009), suggesting that antioxidants might have a beneficial effect against brain aging if administered chronically. Considering the accumulation of oxidative damage as a long-term and continuous process, the protection of antioxidants by scavenging ROS might be a long-time result and preventive effect.…”

“…6C,D), suggesting that the difference may be attributed to the reduction of protein-bound thiol oxidation, not the scavenging of oxygen free radicals. Previous studies have illuminated that chronic administration of antioxidants could attenuate aging-related cognitive disorders (Clausen et al ;Fukui et al, 2002;Head, 2009). However, this study did not show any acute effect of antioxidants on LTP impairment of aged rats.…”

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

“…These abnormalities are also observed in both old rats and vitamin E-deficient young rats not subjected to oxidative stress [9]. Morphological changes in the brain caused by oxidative stress have shown that, in rats subjected to hyperoxia, synaptic vesicles containing neurotransmitters abnormally accumulate in nerve terminals, resulting in a marked reduction in the level of acetylcholine released from synapses [10].…”

“…ROS generated by chronic oxidative stress which is experienced over a long period may attack the brain, leading to aging and neurodegeneration [20]. In fact, young rats subjected to hyperoxia as oxidative stress and normal aged rats show an increase in the amount of denatured lipids at nerve terminals that is, TBARS and conjugated diene [2], accumulation of amyloid β in the hippocampus, and neuron apoptosis, resulting in deficit in cognition [9,21]. Thus, reactive products of lipid peroxidation have been considered for long time to be a causal factor of neurodegenerative diseases.…”

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

“…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.…”