Long-term antioxidant supplementation attenuates oxidative stress markers and cognitive deficits in senescent-accelerated OXYS rats
Long-term antioxidant supplementation attenuates oxidative stress markers and cognitive deficits in senescent-accelerated OXYS rats
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DOI：
10.1016/j.neurobiolaging.2005.07.022
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发表时间：
2006-09-01
影响因子：
4.2
通讯作者：
Loskutova, L. V.
中科院分区：
文献类型：
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作者：
Kolosova, N. G.;Shcheglova, T. V.;Loskutova, L. V.
生物分子的氧化损伤随着年龄的增长而增加，被认为是各种神经退行性疾病的主要原因。因此，抗氧化剂保护神经的概念应运而生。最近，我们已经证明，年轻的加速衰老的OXY大鼠的行为类似于老年Wistar动物的行为。为了确定氧化应激在这一现象中的作用，我们研究了OXY和Wistar大鼠脑内蛋白质羰基(PRC)、过氧化脂质(LP)、还原型谷胱甘肽(GSH)、α-生育酚(TP)和超氧化物歧化酶(SOD)活性随年龄的变化。我们还研究了长期补充越橘提取物(2g/kg饲料)和维生素E(140 mg/kg饲料)对氧化应激标志物和被动回避实验学习的影响。在两个品系的大鼠中，Lp、Prc和TP都随着年龄的增长而增加，24月龄时OXY大鼠的Pcc显著高于对照组(p<；0.0001)。3个月时OXS大鼠GSH高于Wistar大鼠，而SOD活性低于Wistar大鼠。在OXY中，超氧化物歧化酶活性随年龄增长而降低，而在Wistar大鼠中随年龄增长而升高。OXYS大鼠的认知损害早于两个品系之间大脑氧化应激标志物水平的显著差异。相比之下，Wistar和OXYS大鼠的抗氧化系统在3个月时就出现了差异。抗氧化剂减轻OXYS大鼠的认知障碍，为抗氧化剂的治疗作用提供了证据。然而，体内抗氧化剂神经保护作用的确切机制以及氧化应激对OXY大鼠认知障碍发展的真正影响仍需进一步研究。(C)2005 Elsevier Inc.保留所有权利。
Oxidative damage of biomolecules increases with age and is postulated to be a major causal factor of various neurodegenerative disorders. Consequently, the concept of neuroprotection by antioxidants has been developed. Recently we have shown that the behaviour of young senescent-accelerated OXYS rats is similar to the behaviour of old Wistar animals. To determine the role of oxidative stress in this phenomenon we investigated age-related changes in protein carbonyls (PrC), lipid peroxides (LP), reduced glutathione (GSH), alpha-tocopherol (TP) and SOD activity in the brain of OXYS and Wistar rats. We also studied the effect of long-term supplementation with bilberry extract (2 g/kg of diet) and Vitamin E (140 mg/kg of diet) on oxidative stress markers and on learning in passive avoidance test. In both rat strains LP, PrC and TP increased with age and at 24 months PrC was significantly higher (p < 0.0001) in OXYS rats. At 3 months GSH was higher and SOD activity was lower in OXYS rats than in Wistar rats. SOD activity decreased with age in OXYS whereas increased in Wistar rats. Cognitive impairments in OXYS rats were manifested earlier than significant differences in the level of brain oxidative stress markers between two strains. By contrast, differences in antioxidant systems of Wistar and OXYS rats were registered at 3 months. Antioxidants attenuated cognitive deficits in OXYS rats, providing evidence for therapeutic role of antioxidants. Nevertheless, the exact mechanisms of neuroprotective effects of antioxidants in vivo and the real impact of oxidative stress on the development of cognitive impairments in OXYS rats still needs to be further investigated. (c) 2005 Elsevier Inc. All rights reserved.