Ablating Adult Neural Stem Cells Improves Synaptic and Cognitive Functions in Alzheimer Models
Xiaoqin Zhang, Yufei Mei, Yang He, Dongpi Wang, Jing Wang, Xiaojie Wei, Enlu Yang, Dongming Zhou, Haowei Shen, Guoping Peng, Qiang Shu, Xuekun Li, Benyan Luo, Yudong Zhou, Binggui Sun
Abstract
Adult neurogenesis is impaired in the hippocampus of patients with Alzheimer disease (AD) as well as AD models. However, it is far from clear how modulating adult neurogenesis affects AD neuropathology. We confirm that adult hippocampal neurogenesis is impaired in two AD models. Surprisingly, however, cognitive functions are improved in AD models after ablating adult neural stem cells (aNSCs). Ablation of aNSCs does not affect the levels of amyloid β but restores the normal synaptic transmission in the dentate gyrus (DG) granule cells of AD models. Furthermore, calbindin depletion in the DG of AD mice is ameliorated after aNSC ablation, and knocking down calbindin abolishes the effects of aNSC ablation on synaptic and cognitive functions of AD mice. Together, our data suggest that cognitive functions of AD mice are improved after aNSC ablation, which is associated with the restoration of synaptic transmission in the DG granule cells with calbindin as an important mediator.