Neural stem cells improve the function of learning and memory in the ibotenic acid-induced Alzheimer's disease mice.

Abstract

Neural stem cells (NSCs) showed a promising approach to treat Alzheimer's disease (AD). This study aims to investigate whether mouse NSCs transplantation can improve the function of learning and memory of AD mouse model and the underlying mechanism. NSCs was stereotaxically injected into the hippocampi of ibotenic acid (IBO)-induced AD mice. Behavioral tests were conducted to evaluate neurological function. Golgi and immunofluorescence staining were used to assess the injury of the nerves. Additionally, enhanced green fluorescent protein (EGFP) labeling was employed to evaluate the differentiation of NSCs. Compared with model group, NSCs transplantation shortened the escape latency and increased the crossing platform quadrant time, number of crossing the platform (p&#x202f;<&#x202f;0.01). The preference index and active avoidance rate was increased after NSCs transplantation when compared with the model group (p&#x202f;<&#x202f;0.05 or p&#x202f;<&#x202f;0.01). NSCs augmented not only the number of neurons in the hippocampal CA1 region, but also the dendritic spine density, dendritic complexity and ACh content in the hippocampus (p&#x202f;<&#x202f;0.05 or p&#x202f;<&#x202f;0.01). Furthermore, NSCs also elevated the levels of BDNF in the hippocampus of AD mice (p&#x202f;<&#x202f;0.01). It also showed that a portion of transplanted NSCs differentiated into neurons at four weeks post-transplantation. These results demonstrated that NSCs improved learning and memory function in the AD model by ameliorating neuron injury and differentiating into neurons.