Levodopa ameliorates learning and memory deficits in a murine model of Alzheimer's disease
Levodopa ameliorates learning and memory deficits in a murine model of Alzheimer's disease
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DOI：
10.1016/j.neurobiolaging.2007.11.010
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发表时间：
2009-08-01
影响因子：
4.2
通讯作者：
Schaebitz, Wolf-Ruediger
中科院分区：
文献类型：
--
作者：
Ambree, Oliver;Richter, Helene;Schaebitz, Wolf-Ruediger
多巴胺在学习和记忆过程中起着重要作用。这种神经递质的缺陷，因为它是明显的阿尔茨海默氏病（AD）可能会导致认知能力下降，AD患者的主要症状。本研究的目的是阐明多巴胺能系统的刺激是否会导致AD小鼠模型中认知功能的改善和非认知行为改变的减少。TgCRND 8系的转基因和野生型雄性小鼠用多巴胺前体左旋多巴或载体处理，并在两个学习任务中进行测试，对象识别任务和巴恩斯迷宫测试。此外，分析了在饲养笼中的24小时自发行为，在两个记忆任务中，野生型小鼠的表现显着优于转基因小鼠。然而，与载体处理的转基因相比，用左旋多巴处理的转基因显示出显著的物体识别记忆和在巴恩斯迷宫中改善的空间记忆获得。关于自发行为，转基因小鼠比野生型小鼠表现出更多的刻板行为。然而，左旋多巴组在药物有效期内的刻板印象有减少的趋势。神经化学分析显示，与野生型小鼠相比，转基因小鼠的新纹状体和额叶皮质多巴胺水平升高，大脑皮层多巴胺水平降低。因此，认知缺陷和刻板印象可能是由于多巴胺能系统的变化，因为它们可以通过左旋多巴治疗得到改善，这也可能对AD具有治疗意义。(C)2007爱思唯尔公司All rights reserved.
Dopamine plays an important role in learning and memory processes. A deficit of this neurotransmitter as it is apparent in Alzheimer's disease (AD) may contribute to cognitive decline, a major symptom of AD patients. The aim of this study was to elucidate whether or not stimulation of the dopaminergic system leads to an improvement of cognitive function and reduction of non-cognitive behavioral alterations in a murine model of AD.Transgenic and wild type male mice of the TgCRND8 line were treated either with the dopamine precursor levodopa or vehicle and tested in two learning tasks, the object-recognition task and the Barnes maze test. Additionally 24 h spontaneous behavior in the home cage was analyzed.In both memory tasks wild type mice performed significantly better than transgenics. However, transgenics treated with levodopa showed a significant object recognition memory and improved acquisition of spatial memory in the Barnes maze compared to vehicle treated transgenics. Concerning spontaneous behavior transgenic mice performed much more stereotypies than wild types. However, there was a trend for reduced stereotypies in the levodopa group in the time the drug was active. Neurochemical analysis revealed elevated levels of dopamine in the neostriata and frontal cortices and reduced levels in the hippocampi of transgenic mice compared to wild types. Thus cognitive deficits and stereotypies may be due to changes in the dopaminergic system as they could be ameliorated by levodopa treatment, that might also have a therapeutic significance for AD. (C) 2007 Elsevier Inc. All rights reserved.