Chacon-De-La-Rocha Irene, Fryatt Gemma, Rivera Andrea D, Verkhratsky Alexei, Raineteau Olivier, Gomez-Nicola Diego, Butt Arthur M
School of Pharmacy and Biomedical Sciences, Institute of Biomedical and Biomolecular Sciences, University of Portsmouth, Portsmouth, United Kingdom.
School of Biological Sciences, Southampton General Hospital, University of Southampton, Portsmouth, United Kingdom.
Front Cell Neurosci. 2020 Dec 3;14:575082. doi: 10.3389/fncel.2020.575082. eCollection 2020.
Myelin disruption is a feature of natural aging and Alzheimer's disease (AD). In the CNS, myelin is produced by oligodendrocytes, which are generated throughout life by oligodendrocyte progenitor cells (OPCs). Here, we examined age-related changes in OPCs in APP/PS1 mice, a model for AD-like pathology, compared with non-transgenic (Tg) age-matched controls. The analysis was performed in the CA1 area of the hippocampus following immunolabeling for NG2 with the nuclear dye Hoescht, to identify OPC and OPC sister cells, a measure of OPC replication. The results indicate a significant decrease in the number of OPCs at 9 months in APP/PS1 mice, compared to age-matched controls, without further decline at 14 months. Also, the number of OPC sister cells declined significantly at 14 months in APP/PS1 mice, which was not observed in age-matched controls. Notably, OPCs also displayed marked morphological changes at 14 months in APP/PS1 mice, characterized by an overall shrinkage of OPC process domains and increased process branching. The results indicate that OPC disruption is a pathological sign in the APP/PS1 mouse model of AD.
髓鞘破坏是自然衰老和阿尔茨海默病（AD）的一个特征。在中枢神经系统中，髓鞘由少突胶质细胞产生，而少突胶质细胞在整个生命过程中由少突胶质前体细胞（OPC）生成。在此，我们研究了APP/PS1小鼠（一种具有AD样病理特征的模型）中OPC与年龄匹配的非转基因（Tg）对照相比与年龄相关的变化。在用核染料Hoechst对NG2进行免疫标记后，在海马体的CA1区域进行分析，以识别OPC及其姐妹细胞，这是一种衡量OPC增殖的指标。结果表明，与年龄匹配的对照相比，APP/PS1小鼠在9个月时OPC数量显著减少，在14个月时没有进一步下降。此外，APP/PS1小鼠在14个月时OPC姐妹细胞数量显著下降，而在年龄匹配的对照中未观察到这种情况。值得注意的是，APP/PS1小鼠在14个月时OPC也表现出明显的形态变化，其特征是OPC突起区域整体缩小且突起分支增加。结果表明，OPC破坏是AD的APP/PS1小鼠模型中的一种病理标志。
