Selegiline protects against recognition memory impairment induced by neonatal iron treatment
Selegiline protects against recognition memory impairment induced by neonatal iron treatment
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DOI：
10.1016/j.expneurol.2005.07.017
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发表时间：
2005-11-01
影响因子：
5.3
通讯作者：
Schröder, N
中科院分区：
文献类型：
--
作者：
de Lima, MNM;Laranja, DC;Schröder, N
脑中过量的铁与几种人类神经退行性疾病的发病机制有关，例如阿尔茨海默病和帕金森病。研究表明，新生儿期对于成人脑中正常铁含量的建立至关重要。此外，众所周知，衰老会改变这种金属在大脑中的分布。我们最近描述了新生儿铁严重损害大鼠的新物体识别记忆。本研究的目的是确定是否司来吉兰，单胺氧化酶（MAO）抑制剂已知其神经保护特性，可以保护大鼠对新生儿铁管理引起的认知障碍。在第一个实验中，雄性Wistar大鼠从出生后第12至14天经口接受溶剂（5%山梨醇水溶液）或铁（10.0 mg/kg），并在首次铁给药前24小时开始腹膜内注射生理盐水（0.9% NaCl）或司来吉兰（1.0或10.0 mg/kg），持续21天。在第二个实验中，从出生后第12至14天经口给予大鼠溶剂或铁（10.0 mg/kg），随后腹腔内给予盐水或司来吉兰（1.0或10.0 mg/kg），持续21天，从大鼠成年时（出生后第50天）开始。两种剂量的司来吉兰给铁处理的大鼠在识别记忆方面没有表现出缺陷。接受铁但不接受司来吉兰的大鼠出现记忆缺陷。这是第一项报告铁诱导的记忆障碍逆转的研究，支持我们的模型可以被认为是寻找具有神经保护和/或记忆增强特性的新药的有用工具的观点。(c)2005年爱思唯尔公司All rights reserved.
Excess of iron in the brain has been implicated in the pathogenesis of several human neurodegenerative diseases, for example Alzheimer's disease and Parkinson's disease. It has been shown that the neonatal period is critical for the establishment of normal iron content in the adult brain. Moreover, it is known that aging alters the cerebral distribution of this metal. We have recently described that neonatal administration of iron severely impaired novel object recognition memory in rats. The aim of the present study was to determine whether selegiline, a monoamine oxidase (MAO) inhibitor known for its neuroprotective properties, could protect rats against cognitive impairment induced by neonatal administration of iron. In the first experiment, male Wistar rats received vehicle (5% sorbitol in water) or iron (10.0 mg/kg) orally from postnatal days 12 to 14 and saline (0.9% NaCl) or selegiline (1.0 or 10.0 mg/kg) intraperitoneally for 21 days, starting 24 h before the first iron dosing. In the second experiment, rats were given either vehicle or iron (10.0 mg/kg) orally from postnatal days 12 to 14 followed by saline or selegiline (1.0 or 10.0 mg/kg) intraperitoneally for 21 days, starting when rats reached adulthood (50th day after birth). Iron-treated rats given selegiline in both doses showed no deficits in recognition memory. Rats receiving iron but no selegiline presented memory deficits. This is the first study reporting the reversion of iron-induced memory impairment, supporting the view that our model can be considered as a useful tool in the search for new drugs With neuroprotective and/or memory enhancing properties. (c) 2005 Elsevier Inc. All rights reserved.