Nerve growth factor injections administered intranasally combined with exercise can improve learning and memory

Abstract

Objective To investigate the effect of nerve growth factor (NGF) combined with exercise training on nerve protection, learning and memory. Methods Twenty-four six-month-old APP/PS1 mice were randomly divided into a control group, an NGF group, an exercise group and an NGF combined with exercise training group (the combined group), each of 6. The control group mice were given 50 μL of saline intra-nasally every day, while the NGF group were given 50 μL of NGF solution (0.1 mg/ml) intranasally. The exercise group was given 50 μL of saline intra-nasally plus 30 minutes of treadmill exercise daily, while the combined group was given 50 μL of the NGF solution and 30 minutes of exercise. The intervention lasted 21 days. Then Morris water maze test was conducted to evaluate the memory of all groups, and all of the mice were sacrificed and immunohistochemical staining was used to check the levels of APP, Ki-67 expression in cortex and NeuN expression in hippocampus. Results In the place navigation test, significant differences in escape latency were observed among the 4 groups, with the NGF, exercise and combined groups showing average latencies significantly shorter than that of the control group The average latency of the combined group was also significantly shorter than that of the NGF and exercise groups. In the spatial probe, there were significant differences among the 4 groups in the percentage of time spent in the target quadrant. The combined group′s average was significantly larger than those of the NGF and exercises groups. The immunochemistry showed that the combined group had better-arranged neurons and more cells compared with the 3 other groups. The average APP protein expression of the combined group was significantly lower than that of the other groups, but their Ki-67-positive and NeuN-positive cells were found to be significantly more numerous. Conclusion NGF combined with exercise can improve learning and memory, at least in APP/ PS1 mice. This might be associated with its reducing the expression of APP and promoting the expression of Ki-67 and NeuN. Key words: Alzheimer′s disease; Nerve growth factors; Exercise; Learning ability; Memory