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重复进行空间记忆任务可改善 APP/PS1 小鼠的认知能力下降。

Repeated performance of spatial memory tasks ameliorates cognitive decline in APP/PS1 mice.

机构信息

Department of Cellular Neurobiology, Zoological Institute, TU Braunschweig, 38106 Braunschweig, Germany.

Department of Cellular Neurobiology, Zoological Institute, TU Braunschweig, 38106 Braunschweig, Germany; Helmholtz Centre for Infection Research, Neuroinflammation and Neurodegeneration Group, 38124 Braunschweig, Germany.

出版信息

Behav Brain Res. 2023 Feb 13;438:114218. doi: 10.1016/j.bbr.2022.114218. Epub 2022 Nov 17.

Abstract

BACKGROUND

Alzheimer's disease (AD) is a burden on the public health system because it is a neurodegenerative disease that is incurable and for which there is no successful treatment. AD patients suffer from symptoms for many years, with progressive loss of cognitive and functional abilities. In addition to the features of AD, described as amyloid plaques and neurofibrillary tangles, neuroinflammatory processes, genetic factors, and lifestyle also play important roles. Increasing evidence for lifestyle factors includes possible changes due to smoking, social engagement, and physical activity.

METHODS

Morris water maze behavioral tasks were performed to analyze the formation of spatial memory. APPswe/PS1dE9 mice with a remarkable increase in amyloid-β production associated with certain behavioral abnormalities comparable to AD symptoms and age-matched wild-type littermates were trained several times at 3, 6, 9, and 12 months of age and compared with untrained groups at 9 and 12 months of age. Performance during the acquisition phase, in the reference memory test, and in searching strategies were analyzed.

RESULTS

9- and 12-month-old APP/PS1 mice showed cognitive impairment, especially in the reference memory test and searching strategies. This cognitive deterioration was reversed in 9- and 12-month-old APP/PS1 mice that had been previously trained several times. Even in the reversal test, in which memory formation must be adapted to the new platform position, several trained APP/PS1 mice performed better.

CONCLUSION

Repeated spatial memory training in the water maze showed positive effects on memory formation in APP/PS1 mice. Interestingly, the cohort that had been previously trained several times was able to use increased hippocampus-dependent strategies, similar to the WT mice. This may suggest that cognitively demanding and physically active tasks can improve cognitive function.

摘要

背景

阿尔茨海默病(AD)给公共卫生系统带来了负担,因为它是一种无法治愈的神经退行性疾病,目前还没有有效的治疗方法。AD 患者会出现多年的症状,认知和功能能力逐渐丧失。除了 AD 的特征,如淀粉样斑块和神经原纤维缠结,神经炎症过程、遗传因素和生活方式也起着重要作用。越来越多的生活方式因素的证据包括由于吸烟、社交参与和体育活动可能发生的变化。

方法

通过 Morris 水迷宫行为任务分析空间记忆的形成。APPswe/PS1dE9 小鼠表现出明显增加的淀粉样β产生,与 AD 症状和年龄匹配的野生型同窝仔鼠相比具有某些行为异常,可用于模拟 AD 症状。将这些 APPswe/PS1dE9 小鼠在 3、6、9 和 12 个月龄时进行多次训练,并与 9 和 12 个月龄时的未训练组进行比较。分析其在获得阶段的表现、参考记忆测试以及搜索策略。

结果

9 个月和 12 个月大的 APP/PS1 小鼠表现出认知障碍,特别是在参考记忆测试和搜索策略中。这种认知恶化在之前经过多次训练的 9 个月和 12 个月大的 APP/PS1 小鼠中得到了逆转。即使在反转测试中,必须根据新的平台位置重新形成记忆,几个经过训练的 APP/PS1 小鼠也表现更好。

结论

在水迷宫中进行重复的空间记忆训练对 APP/PS1 小鼠的记忆形成有积极影响。有趣的是,之前经过多次训练的队列能够使用更多的海马依赖策略,类似于 WT 小鼠。这可能表明认知要求高和身体活跃的任务可以改善认知功能。

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