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更快的遗忘导致PDAPP小鼠空间记忆受损:记忆提取缺陷与对干扰的敏感性增加有关?

Faster forgetting contributes to impaired spatial memory in the PDAPP mouse: deficit in memory retrieval associated with increased sensitivity to interference?

作者信息

Daumas Stephanie, Sandin Johan, Chen Karen S, Kobayashi Dione, Tulloch Jane, Martin Stephen J, Games Dora, Morris Richard G M

机构信息

Centre for Cognitive and Neural Systems University of Edinburgh, Edinburgh EH8 9JZ, Scotland.

出版信息

Learn Mem. 2008 Aug 26;15(9):625-32. doi: 10.1101/lm.990208. Print 2008 Sep.

Abstract

Two experiments were conducted to investigate the possibility of faster forgetting by PDAPP mice (a well-established model of Alzheimer's disease as reported by Games and colleagues in an earlier paper). Experiment 1, using mice aged 13-16 mo, confirmed the presence of a deficit in a spatial reference memory task in the water maze by hemizygous PDAPP mice relative to littermate controls. However, after overtraining to a criterion of equivalent navigational performance, a series of memory retention tests revealed faster forgetting in the PDAPP group. Very limited retraining was sufficient to reinstate good memory in both groups, indicating that their faster forgetting may be due to retrieval failure rather than trace decay. In Experiment 2, 6-mo-old PDAPP and controls were required to learn each of a series of spatial locations to criterion with their memory assessed 10 min after learning each location. No memory deficit was apparent in the PDAPP mice initially, but a deficit built up through the series of locations suggestive of increased sensitivity to interference. Faster forgetting and increased interference may each reflect a difficulty in accessing memory traces. This interpretation of one aspect of the cognitive deficit in human mutant APP mice has parallels to deficits observed in patients with Alzheimer's disease, further supporting the validity of transgenic models of the disease.

摘要

进行了两项实验,以研究携带突变淀粉样前体蛋白(PDAPP)的小鼠(如Games及其同事在早期论文中报道的,是一种成熟的阿尔茨海默病模型)遗忘速度更快的可能性。实验1使用13 - 16月龄的小鼠,证实了相对于同窝对照,半合子PDAPP小鼠在水迷宫空间参考记忆任务中存在缺陷。然而,在过度训练至同等导航性能标准后,一系列记忆保持测试显示PDAPP组遗忘速度更快。非常有限的再训练就足以使两组小鼠恢复良好的记忆,这表明它们更快的遗忘可能是由于提取失败而非痕迹消退。在实验2中,要求6月龄的PDAPP小鼠和对照小鼠学习一系列空间位置,直至达到标准,并在学习每个位置后10分钟评估它们的记忆。最初,PDAPP小鼠没有明显的记忆缺陷,但在一系列位置学习过程中缺陷逐渐显现,提示对干扰的敏感性增加。更快的遗忘和对干扰敏感性增加可能都反映了在获取记忆痕迹方面存在困难。对人类突变淀粉样前体蛋白小鼠认知缺陷这一方面的这种解释与阿尔茨海默病患者中观察到的缺陷相似,进一步支持了该疾病转基因模型的有效性。

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