Wu Yu, Ma Yuanlin, Liu Zhuo, Geng Qi, Chen Zexin, Zhang Yan
State Key Laboratory of Membrane Biology, College of Life Sciences, PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, 100871, China.
State Key Laboratory of Membrane Biology, College of Life Sciences, PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, 100871, China; College of Forensic Science, People's Public Security University of China, Beijing, China.
Neurosci Lett. 2017 Mar 6;642:102-106. doi: 10.1016/j.neulet.2017.02.007. Epub 2017 Feb 6.
Alzheimer's disease (AD) is the most common cause to dementia and predicted to influence about 35 million people by the end of 2050. In this study, we discover alterations of myelin morphology in hippocampus tissues of 2-month-old APP/PS1 mouse. Myelin sheath is thicker and internodal distance is shorter in APP/PS1 mouse. Oligodendrocytes, differentiated from oligodendrocytes progenitor cells (OPCs), are responsible for formation and maintenance of myelin sheath in central nervous system (CNS). Our current results demonstrate that the oligodendrocytes development is disordered in 2-month-old APP/PS1 mouse. Neuregulin-1 type III, which is critical for both oligodendrocytes development and CNS myelination, is found up-regulated in hippocampus tissues of APP/PS1 mouse by western blots. Furthermore, we find active-caspase-6 can cleave neuregulin-1 type III at the cytoplasmic region. Given together, this study indicates the alterations of myelin morphology and oligodendrocytes development in 2-month-old APP/PS1 mouse, and the alterations might be highly associated with neuregulin-1 type III and active-caspase-6.
阿尔茨海默病(AD)是导致痴呆的最常见原因,预计到2050年底将影响约3500万人。在本研究中,我们发现2月龄APP/PS1小鼠海马组织中髓鞘形态发生改变。APP/PS1小鼠的髓鞘更厚,节间距离更短。少突胶质细胞由少突胶质前体细胞(OPC)分化而来,负责中枢神经系统(CNS)中髓鞘的形成和维持。我们目前的结果表明,2月龄APP/PS1小鼠的少突胶质细胞发育紊乱。通过蛋白质免疫印迹法发现,对少突胶质细胞发育和CNS髓鞘形成至关重要的Ⅲ型神经调节蛋白-1在APP/PS1小鼠海马组织中上调。此外,我们发现活化的半胱天冬酶-6可以在细胞质区域切割Ⅲ型神经调节蛋白-1。综合来看,本研究表明2月龄APP/PS1小鼠存在髓鞘形态和少突胶质细胞发育的改变,且这些改变可能与Ⅲ型神经调节蛋白-1和活化的半胱天冬酶-6高度相关。