Alterations of myelin morphology and oligodendrocyte development in early stage of Alzheimer's disease mouse model.
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.
State Key Laboratory of Membrane Biology, College of Life Sciences, PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, 100871, China.
Yu
Y
Wu
State Key Laboratory of Membrane Biology, College of Life Sciences, PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, 100871, China.
Yuanlin
Y
Ma
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.
Zhuo
Z
Liu
State Key Laboratory of Membrane Biology, College of Life Sciences, PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, 100871, China.
Qi
Q
Geng
State Key Laboratory of Membrane Biology, College of Life Sciences, PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, 100871, China.
Zexin
Z
Chen
State Key Laboratory of Membrane Biology, College of Life Sciences, PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, 100871, China. Electronic address: yanzhang@pku.edu.cn.
Yan
Y
Zhang
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D053178:Caspase 6 / Q000378:metabolism; D004195:Disease Models, Animal; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D009186:Myelin Sheath / Q000378:metabolism / Q000473:pathology*; D020890:Neuregulin-1 / Q000378:metabolism; D009836:Oligodendroglia / Q000378:metabolism / Q000473:pathology*; D053764:Presenilin-1 / Q000235:genetics
D016564:Amyloid beta-Protein Precursor; D020890:Neuregulin-1; D053764:Presenilin-1; D053178:Caspase 6
Active-caspase-6; Alzheimer’s disease; Myelination; Neuregulin I type III; Oligodendrocyte