The effect of combining transplanted neural stem cells with neural growth factors on synaptophysin levels and behavior / 中华物理医学与康复杂志

ABSTRACT

Objective:To observe the effect of transplanting neural stem cells (NSCs) and nerve growth factor (NGF) nanoparticles on hippocampal synaptophysin (SYN) levels in APP/PS1 double-transgenic mice and on their behavior.Methods:NSCs from the brains of transgenic mouse fetuses were cultured in vitro. Twenty-four 12-month-old male APP/PS1 mice with Alzhaimer′s disease (AD ) were randomly divided into an NSC combined with NGF transplantation group (NSCs+ NGF-NP group), an NSC transplantation group (NSCs group) and an AD control group (AD group), each of 8. Another 8 healthy male counterparts formed a normal control group (WT group). The rats in the NSCs+ NGF-NP and NSCs groups had NSCs combined with NGF nanoparticles or NSCs alone injected into their brains, while the bilateral hippocampi of the other two groups were injected with the same volume of phosphate buffer. Four weeks later the Morris water maze test was used to quantify the rats′ learning and memory functioning. The migration and differentiation of the transplanted cells were measured using fluorescence immunohistochemistry, while the level of synaptophysin protein in the hippocampus was detected using western blotting.Results:Neurospheres cultured in vitro showed positive expression of enhanced green fluorescent protein(EGFP) and nestin, which are specific markers of neural stem cells. Four weeks after the transplantation, cells traced using EGFP had survived and migrated to the corpus callosum and deep into the hippocampus and dentate gyrus. Transplanted cells had differentiated into DCX-positive neurons and GFAP-positive glial cells. The samples from the NSCs+ NGF-NP group showed a larger number of viable cells with longer protrusions, and some had crossed the hippocampal granular layer. The average synaptophysin levels in the WT, NSCs and NSCs+ NGF-NP groups were significantly higher than that of the AD group. The average synaptophysin level of the NSCs+ NGF-NP group was significantly higher than in the NSCs group but not significantly different from the WT group′s average. The Morris water maze results showed that compared with the AD group the time in the platform quadrant and the platform crossing times increased significantly in the WT, NSCs and NSCs+ NGF-NP groups. The average platform crossing time of the NSCs+ NGF-NP group was greater than that of the NSCs group but not significantly different from the WT group′s average.Conclusion:Injecting NSCs combined with NGF nanoparticles can promote the survival and maturation of the transplanted cells in vivo, increase hippocampal synapses, and thus improve learning and memory, at least in AD mice.