Deleting Adult Neural Stem Cells Ameliorates Synaptic and Cognitive Deficits in Animal Models of Alzheimer's Disease

Abstract

The development of adult neural stem cells (aNSCs) was impaired in the hippocampus of animal models of Alzheimer’s disease (AD). However, whether and how aNSCs and new neurons derived from aNSCs affect AD neuropathology is unclear. Here, we found that genetic or drug-induced ablation of aNSCs significantly ameliorated deficits of synaptic plasticity and cognitive functions in two mouse models of AD. On the other hand, whole cell recording revealed that deleting aNSCs prevented the increased inhibition in the dentate granule cells of AD mice. Furthermore, deleting aNSCs did not affect Aβ levels but prevented the calbindin depletion in the hippocampus of AD mice. Knocking down calbindin in the hippocampus abolished the effects of deleting aNSCs on synaptic and cognitive functions in AD mice. Taken together, our data suggest that deleting aNSCs improved synaptic plasticity and cognitive functions in AD mice by regulating the activity of dentate granule cells via calbindin.