Recognition memory impairment and brain oxidative stress induced by postnatal iron administration
Recognition memory impairment and brain oxidative stress induced by postnatal iron administration
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DOI：
10.1111/j.1460-9568.2005.04083.x
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发表时间：
2005-05-01
影响因子：
3.4
通讯作者：
Schröder, N
中科院分区：
文献类型：
--
作者：
de Lima, MNM;Polydoro, M;Schröder, N
大脑中的铁积累与神经退行性疾病的发病机制有关。众所周知，铁催化形成高活性的羟基自由基。最近的研究表明，氧化损伤与大鼠和人类的记忆缺陷有关。本研究旨在探讨新生儿期四个不同阶段的铁治疗对大鼠再认记忆的长期影响。此外，还评估了与记忆形成相关的大脑区域的氧化应激参数。雄性Wistar大鼠在出生后第5~7天、12~14天、19~21天或30~32天灌胃给予溶剂或10.0 mg/kg的Fe2+。在新生儿期的任何阶段给予铁的动物在物体识别记忆的长期保持方面都显示出障碍，尽管只有出生后12-14天给予铁的那一组表现出完全的记忆阻断。通过硫代巴比妥酸反应物种分析，铁处理导致了大脑的氧化损伤。此外，补铁增加了亚线粒体颗粒中超氧化物的生成，表明线粒体功能受损；而且易受补铁影响的大脑区域的超氧化物歧化酶活性增加。结果表明，生命早期的铁负荷可能通过诱导大脑氧化损伤而导致认知损害。这些发现与氧化应激可能与正常衰老中观察到的认知能力下降有关的观点是一致的。
Iron accumulation in the brain has been implicated in the pathogenesis of neurodegenerative disorders. It is known that iron catalyses the formation of highly reactive hydroxyl radicals. Recent studies have implicated oxidative damage in memory deficits in rats and humans. The purpose of the present study was to investigate the long-term effects of iron treatment in four different phases of the neonatal period on recognition memory in rats. Additionally, parameters of oxidative stress in cerebral regions related to memory formation were evaluated. Male Wistar rats received vehicle or 10.0 mg/kg of Fe2+ orally at postnatal days 5-7, 12-14, 19-21 or 30-32. Animals given iron at any phase of the neonatal period showed impairments in long-term retention of object recognition memory, although only the group given iron from postnatal days 12-14 showed a complete memory blockade. Iron treatment induced oxidative damage in the brain as assessed by the thiobarbituric acid reactive species assay. Moreover, iron administration increased superoxide production in submitochondrial particles, suggesting impaired mitochondrial function; and there was an increase in superoxide dismutase activity in brain regions susceptible to iron administration. The results show that iron load in the early stages of life induces cognitive impairment possibly by inducing oxidative damage in the brain. These findings are consistent with the view that oxidative stress may be related to the cognitive decline observed in normal ageing.