唐氏综合征和唐氏综合征和阿尔茨海默病小鼠模型中miR-146a和miR-155的发育表达和调控

Title:Developmental Expression and Dysregulation of miR-146a and miR-155 in Down's Syndrome and Mouse Models of Down's Syndrome and Alzheimer's Disease

Volume: 14 Issue: 12

关键词: 海马，发育，唐氏综合症，阿尔茨海默氏病，Ts65Dn-APP / PS1，microRNA。

摘要: Background: miR-146a and miR-155 are key regulators of the innate immune response. We hypothesized that an inflammation-mediated dysregulation of these miRNAs may occur in patients with Down syndrome (DS) and Alzheimer's disease (AD).

Methods: The miRNA expression patterns were investigated by in situ hybridization in developing hippocampus from controls, patients with DS and in adults with AD pathology (DS and sporadic AD; sAD). Quantitative real-time PCR was employed to evaluate the miRNA levels in the hippocampus of sAD and in mouse models of DS and AD. Both miRNAs were expressed in prenatal human hippocampus. In DS we detected increased miR-146a expression in reactive astrocytes. Increased expression of miR-146a was found in the hippocampus of sAD and negatively correlated with its target IRAK-1. APP/PS1 mice showed a significant increase in the expression of both miRNAs at 11-13 months of age as compared to WT and mice at 3 months. A negative correlation between miR-146a levels and its target TRAF6 was observed in both Ts65Dn and APP/PS1 mice.

Conclusion: These findings suggest a possible involvement of miR-146a and miR-155 in brain development and neurodegeneration. In particular, we provide evidence of a dysregulation of these two immunomodulatory miRNAs in AD with a potential therapeutical implication, deserving further investigation.

Cite this article as:

Developmental Expression and Dysregulation of miR-146a and miR-155 in Down's Syndrome and Mouse Models of Down's Syndrome and Alzheimer's Disease, Current Alzheimer Research 2017; 14 (12) . https://dx.doi.org/10.2174/1567205014666170706112701