The experimental research between magnetic resonance spectroscopy and changes of behavior for neural stem cell transplantation in APP/PS1 transgenic mice

Abstract

Objective To explore the effect of neural stem cell(NSCs) transplantation on proton magnetic resonance spectroscopy (1H-MRS) and the behavior in APP/PS1 double transgenic AD mice. Methods NSCs from C57BL/6 mice were cultured and amplified. APP/PS1 double transgenic AD mice (n=30) aged 12 months were used as the study group, and mild-type mice (n=15) were used as the control group(group C ). Animals in the study group were randomly divided into two subgroups: one receiving NSCs (group A) and the other receiving PBS transplantation (group B) in bilateral hippocampal CA1 of the AD model mice. Animals in the group C were not treated. 1H-MRS and Morris water maze (MWM) were performed before transplantation and 4 weeks after transplantation, and compared with the histopathological results. Results 1H-MRS showed that there was no significant change in NAA/ Cr(1.01±0.08 and 1.03±0.05) and mI/Cr (0.69±0.05 and 0.71±0.06) ratios between group A and group B before transplantation (P> 0.05), but the changes were significant compared with the group C(NAA/ Cr: 1.21±0.05; mI/Cr: 0.58±0.06) (P<0.05). Four weeks after transplantation, NAA/ Cr ratio(1.18±0.09) was increased and mI/ Cr ratio (0.53±0.04) was decreased in group A. The difference was significant compared with the group B at the same time points (P<0.05). MWM showed the escape latency in group A was significantly shorter than that in group B after transplantation (P<0.05). In addition, group A also showed an exclusive preference for the target quadrant, and spent more time((35.21±5.44)s) in the 3rd quadrant compared with group B (P<0.05). For number of platform crossings, similar results were also shown(5.75±3.23). Nissl's staining showed that the number of neurons in the hippocampal area increased more significantly in group A than those in group B(P<0. 05). Conclusion NSCs transplantation can improve spatial learning and memory via neurons regeneration in APP/PS1 double transgenic AD mice, and 1H-MRS is able to display intracranial metabolite changes after NSCs transplantation. Key words: Neural stem cell; Alzheimer disease; Magnetic resonance spectroscopy; Transplantation