Cognitive deficits could be alleviated by transplantation of neural stem cells in animals. Grafted cells may differentiate into neurons, thereby improving animal cognition. Alternatively, grafted cells may provide neurotrophic factors to modify neuronal functions and to alleviate cognitive deficits. To test which mechanism is underlying this recovery process, senescence-accelerated mice were transplanted with human neural stem cells into the hippocampus. The effect of cell transplantation was assessed in the Morris water maze. The survival and differentiation of grafted cells and the expression of NMDA receptors were examined. The data suggested that in addition to the neural differentiation of grafted neural stem cells, up-regulation of NMDA receptors after transplantation also contributed to the alleviation of cognitive deficits in this animal model.