Aggrecan modulates the expression and phosphorylation of tau in a novel bigenic TauP301L - Acan mouse model,European Journal of Neuroscience

当前位置： X-MOL 学术 › Eur. J. Neurosci. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Aggrecan modulates the expression and phosphorylation of tau in a novel bigenic TauP301L - Acan mouse model
European Journal of Neuroscience ( IF 2.7 ) Pub Date : 2020-08-01 , DOI: 10.1111/ejn.14923
Sophie Schmidt ₁ , Caroline Stapf ₁ , Sandra Schmutzler ₁ , Ingolf Lachmann ₂ , Thomas Arendt ₁ , Max Holzer ₁ , Mandy Sonntag ₁ , Markus Morawski ₁

Affiliation

Selected types of neurons in the central nervous system are associated with a specialized form of extracellular matrix. These so-called perineuronal nets (PNs) are supramolecular structures surrounding neuronal somata, proximal dendrites and axon initial segments. PNs are involved in the regulation of plasticity and synaptic physiology. In addition, PNs were proposed to carry neuroprotective functions as PN-ensheathed neurons are mostly spared of tau pathology in brains of Alzheimer patients. Recently, the neuroprotective action of PNs was confirmed experimentally, demonstrating (i) that mainly aggrecan mediates the neuroprotective function of PNs and (ii) that aggrecan seems to generate an external shielding preventing the internalization of pathological forms of tau. In the present study, we aimed at extending these findings and hypothesized that aggrecan further provides an intracellular protection by preventing mutation-triggered formation of pathological forms of tau. We used crossbreds of TauP301L mice and heterozygous aggrecan mice which are characterized by spontaneous deletion of the aggrecan allele. We analysed the extent of tau pathology in dependence of aggrecan protein amount by applying immunohistochemistry, Western blotting and ELISA. The results clearly indicate that aggrecan has no significant impact on tau aggregation in the brainstem of our mouse model. Still, reduced aggrecan levels were accompanied by increased levels of tau protein and reduced number of Tau-1-positive neurons, which indicate an increase in phosphorylation of tau. In conclusion, these data demonstrate a correlation between aggrecan and P301L mutation-triggered tau expression and phosphorylation in our bigenic mouse model.

中文翻译：

Aggrecan 调节新型生物 TauP301L - Acan 小鼠模型中 tau 的表达和磷酸化

中枢神经系统中选定类型的神经元与一种特殊形式的细胞外基质有关。这些所谓的神经周围网 (PN) 是围绕神经元胞体、近端树突和轴突初始节段的超分子结构。PN 参与可塑性和突触生理的调节。此外，PNs 被提议具有神经保护功能，因为 PN 包裹的神经元在阿尔茨海默病患者的大脑中大多不受 tau 病理影响。最近，PNs 的神经保护作用在实验中得到证实，证明 (i) 蛋白聚糖主要介导 PNs 的神经保护功能和 (ii) 蛋白聚糖似乎产生外部屏蔽，防止病理形式的 tau 内化。在目前的研究中，我们旨在扩展这些发现并假设聚集蛋白聚糖通过防止突变触发的病理形式 tau 形成进一步提供细胞内保护。我们使用杂交的 TauP301L 小鼠和杂合子以蛋白聚糖等位基因自发缺失为特征的蛋白聚糖小鼠。我们通过应用免疫组织化学、蛋白质印迹和 ELISA 分析了依赖于聚集蛋白聚糖蛋白量的 tau 病理学程度。结果清楚地表明，聚集蛋白聚糖对我们小鼠模型脑干中的 tau 聚集没有显着影响。尽管如此，蛋白聚糖水平的降低伴随着 tau 蛋白水平的增加和 Tau-1 阳性神经元数量的减少，这表明 tau 的磷酸化增加。总之，这些数据证明了我们的基因小鼠模型中聚集蛋白聚糖和 P301L 突变触发的 tau 表达和磷酸化之间的相关性。

更新日期：2020-08-01

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文本刊介绍/投稿指南11