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衰老和阿尔茨海默病小鼠认知功能的改变与神经免疫功能障碍有关。

Alteration of Cognitive Function in Aging and Alzheimer's Disease Mice Is Related to Dysfunction of the Neuroimmune System.

机构信息

Department of Geriatrics, Renmin Hospital of Wuhan University, Wuhan, China.

Department of Clinical Laboratory, Renmin Hospital of Wuhan University, Wuhan, China.

出版信息

J Alzheimers Dis. 2023;94(2):815-839. doi: 10.3233/JAD-230292.

Abstract

BACKGROUND

Both Alzheimer's disease (AD) and aging have aging-related cognitive dysfunction with a high incidence. These neurological diseases cause serious cognitive problems in patients' daily life. But the cognitive dysfunction mechanism in-depth of aging is far less known than that of AD.

OBJECTIVE

To reveal the different mechanisms of AD and aging-related cognitive dysfunction, we compared the mechanisms of aging and AD through analysis of differentially expressed genes.

METHODS

Mice were divided into four groups (3-month C57BL, 16-month C57BL, 3-month 3xTg AD mice, and 16-month 3xTg AD mice) according to genotype and age. The Morris water maze was employed to investigate the spatial cognition of mice. Differential expressions of genes of AD and aging were analyzed through RNA sequencing and GO, KEGG, Reactome analysis, and the dynamic change trend analysis. Microglia was stained with immunofluorescence and its numbers were counted for analysis.

RESULTS

The cognitive function of elderly mice were worse through testing with the Morris water maze. The cognitive function of 16-month 3xTg AD mice were worse than 16-month C57BL mice. The alteration tendencies of DE genes were uncovered, and microglia numbers increased during aging and AD progression through immunofluorescence.

CONCLUSION

These results suggest that immune-related pathways might play a critical role in aging and AD-related cognitive dysfunction. Our research will help to provide some new potential targets for treating cognitive dysfunction in aging and AD.

摘要

背景

阿尔茨海默病(AD)和衰老都与认知功能障碍有关,且发病率较高。这些神经退行性疾病会导致患者日常生活中出现严重的认知问题。但与 AD 相比,衰老相关认知功能障碍的深入机制知之甚少。

目的

为了揭示 AD 和衰老相关认知功能障碍的不同机制,我们通过分析差异表达基因比较了衰老和 AD 的机制。

方法

根据基因型和年龄将小鼠分为四组(3 月龄 C57BL、16 月龄 C57BL、3 月龄 3xTg AD 小鼠和 16 月龄 3xTg AD 小鼠)。采用 Morris 水迷宫实验检测小鼠的空间认知能力。通过 RNA 测序和 GO、KEGG、Reactome 分析以及动态变化趋势分析,分析 AD 和衰老的差异表达基因。通过免疫荧光染色分析小胶质细胞并计数其数量。

结果

通过 Morris 水迷宫测试发现,老年小鼠的认知功能下降。16 月龄 3xTg AD 小鼠的认知功能比 16 月龄 C57BL 小鼠差。揭示了差异表达基因的变化趋势,并且通过免疫荧光发现衰老和 AD 进展过程中小胶质细胞数量增加。

结论

这些结果表明,免疫相关途径可能在衰老和 AD 相关认知功能障碍中发挥关键作用。我们的研究将有助于为治疗衰老和 AD 相关认知功能障碍提供一些新的潜在靶点。

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