摘要
背景:阿尔茨海默氏症(AD)除了认知能力下降外,还伴有兴奋和活动中断和睡眠障碍。这些症状通常发生在傍晚或晚上,被称为“日落”。他们特别困难的照顾者,也没有具体的药物治疗。越来越多的证据表明,这些症状反映了昼夜节律产生和传播的病理。目的:我们研究的是一个有关AD转基因小鼠模型(APPswe/PS1dE9)表现出昼夜变化在他们的笼子里的自发活动,无论是从这些小鼠离体海马及延髓脑桥脑区参与的昼夜周期的调控生物钟基因表达异常。 结果:在2月龄雌性小鼠APPswe/PS1dE9转基因改变昼夜节律的自发活动水平和模式。的时钟基因Per1、Per2表达CRY1和CRY2发现增加在黑夜与白天比野生型对照小鼠延髓/脑桥。这种效应被减弱为CRY1和CRY2基因表达APPswe/PS1dE9。 结论:本研究显示女性APPswe/PS1dE9小鼠,这改变了生物分子的类比在一个广泛使用的AD的早期年龄,这些影响是显式模型的自发活动昼夜调节改变异常表明这些昼夜节律的影响可能先于斑块的发展。的APPswe/PS1dE9小鼠遗传模型可能有潜在的作为一个工具,了解AD神经病理学和昼夜节律异常作为一个模型系统测试这些症状的新的治疗剂。
关键词: 阿尔茨海默病、昼夜节律、生物钟基因,APPswe/PS1dE9小鼠,PER1,PER2、CRY1和CRY2,Bmal,REV-ERB
Current Alzheimer Research
Title:Abnormal Clock Gene Expression and Locomotor Activity Rhythms in Two Month-Old Female APPSwe/PS1dE9 Mice
Volume: 14 Issue: 8
关键词: 阿尔茨海默病、昼夜节律、生物钟基因,APPswe/PS1dE9小鼠,PER1,PER2、CRY1和CRY2,Bmal,REV-ERB
摘要: Background: In addition to cognitive decline, Alzheimer’s Disease (AD) is also characterized by agitation and disruptions in activity and sleep. These symptoms typically occur in the evening or night and have been referred to as ‘sundowning’. They are especially difficult for carers and there are no specific drug treatments. There is increasing evidence that these symptoms reflect pathology of circadian rhythm generation and transmission.
Objective: We investigated whether a transgenic mouse model relevant to AD (APPswe/PS1dE9) exhibits circadian alterations in locomotor activity in their home cage and whether expression of clock genes involved in the regulation of the circadian cycle is abnormal in the hippocampus and medulla-pons brain regions isolated from these mice. Results: In 2month old female mice the APPswe/PS1dE9 transgene alters levels and patterns in circadian rhythm of locomotor activity. Expression of the clock genes Per1, Per2, Cry1 and Cry2 was found to increase at night compared to day in wild-type control mice in the medulla/pons. This effect was blunted for Cry1 and Cry2 gene expression in APPswe/PS1dE9. Conclusion: This study suggests altered circadian regulation of locomotor activity is abnormal in female APPswe/ PS1dE9 mice and that this alteration has biomolecular analogies in a widely available model of AD. The early age at which these effects are manifest suggests that these circadian effects may precede plaque development. The APPswe/PS1dE9 mouse genetic model may have potential to serve as a tool in understanding the neuropathology of circadian abnormalities in AD and as a model system to test novel therapeutic agents for these symptoms.Export Options
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Cite this article as:
Abnormal Clock Gene Expression and Locomotor Activity Rhythms in Two Month-Old Female APPSwe/PS1dE9 Mice, Current Alzheimer Research 2017; 14 (8) . https://dx.doi.org/10.2174/1567205014666170317113159
DOI https://dx.doi.org/10.2174/1567205014666170317113159 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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Current updates on the Role of Neuroinflammation in Neurodegenerative Disorders
Neuroinflammation is an invariable hallmark of chronic and acute neurodegenerative disorders and has long been considered a potential drug target for Alzheimer?s disease (AD) and dementia. Significant evidence of inflammatory processes as a feature of AD is provided by the presence of inflammatory markers in plasma, CSF and postmortem brain ...read more
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