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在载脂蛋白E小鼠大脑中鉴定已确定进入的阿尔茨海默病基因。

Identifying Alzheimer's disease genes in apolipoprotein E mice brains with confirmed entry.

作者信息

Singhrao Sim K, Consoli Claudia

机构信息

School of Medicine and Dentistry, University of Central Lancashire, Preston, UK.

Central Biotechnology Services, College of Biomedical and Life Sciences, Cardiff University, Wales, UK.

出版信息

J Alzheimers Dis Rep. 2025 Mar 31;9:25424823251332874. doi: 10.1177/25424823251332874. eCollection 2025 Jan-Dec.

Abstract

BACKGROUND

The apolipoprotein E allele ε4 is the most well-known predisposing genetic risk factor for Alzheimer's disease (AD).

OBJECTIVE

To identify AD genes in apolipoprotein E (ApoE) mice brains with confirmed entry of .

METHODS

TaqMan™ Mouse AD arrays were performed on orally infected ApoE mice with confirmed entry and compared with sham infected mice brains (N = 4) at 12- and 24-weeks post infection.

RESULTS

Gene expression by qPCR demonstrated that in the 12-weeks post oral infection, two genes were statistically significantly changed in their expression. These were cyclin dependent kinase 5 regulatory subunit 1 (Cdk5r1, 0.15 logfold change, p = 0.05) and Interleukin 1 alpha, (IL1a, -0.10 log fold change, p = 0.012). In the 24-weeks post oral infection, three genes were statistically significantly changed in their expression. These were cholinergic receptor nicotinic alpha 7 subunit or Chrna7 (0.10 log fold change, p = 0.02), mitogen-activated protein kinase 1 or Mapk1 (0.10 log fold change, p = 0.05) and visinin like 1 or Vnsl1 (0.01 log fold change, p = 0.04). 87 out of 92 AD target genes demonstrated no difference between infected and sham mice brains.

CONCLUSIONS

Five genes, from a recognized AD panel had statistically significantly altered expression in the ApoE mouse AD model following entry into the brain. This suggests the ApoE genetic variation may control the biological activity of specific genes relevant to inflammation and neuronal plasticity following infection.

摘要

背景

载脂蛋白E等位基因ε4是阿尔茨海默病(AD)最著名的遗传易感性风险因素。

目的

在已证实有[病原体名称]进入的载脂蛋白E(ApoE)小鼠大脑中鉴定AD相关基因。

方法

对经口感染且已证实有[病原体名称]进入的ApoE小鼠进行TaqMan™小鼠AD基因芯片检测,并在感染后12周和24周与假感染小鼠大脑(N = 4)进行比较。

结果

qPCR检测基因表达显示,在经口感染后12周,有两个基因的表达发生了统计学显著变化。它们是细胞周期蛋白依赖性激酶5调节亚基1(Cdk5r1,0.15对数倍变化,p = 0.05)和白细胞介素1α(IL1a,-0.10对数倍变化,p = 0.012)。在经口感染后24周,有三个基因的表达发生了统计学显著变化。它们是胆碱能受体烟碱型α7亚基或Chrna7(0.10对数倍变化,p = 0.02)、丝裂原活化蛋白激酶1或Mapk1(0.10对数倍变化,p = 0.05)和类视黄蛋白样1或Vnsl1(0.01对数倍变化,p = 0.04)。92个AD靶基因中有87个在感染小鼠和假感染小鼠大脑之间没有差异。

结论

在[病原体名称]进入大脑后,来自公认的AD基因组合中的五个基因在ApoE小鼠AD模型中的表达发生了统计学显著改变。这表明ApoE基因变异可能在[病原体名称]感染后控制与炎症和神经元可塑性相关的特定基因的生物学活性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23c7/11960171/9d059c5e448e/10.1177_25424823251332874-fig1.jpg

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