Study on the memory cognitive function of neural progenitor cell transplantation with fibrin suppository in Alzheimer's disease model rats and its mechanism

Abstract

Objective To investigate the improvement of memory function and the differentiation ability after transplantation of NPCs with multiple factor to hippocampus in AD model rats. Method Fetal rat NPCs were isolated from C57BL/6J pregnant rats at gestational age of 10 days; AD model mice were divided into three groups: NPCs+ multiple factors group, multiple factors group and PBS group, and The control group is the same age C57BL/6J mouse. Morris water maze (MWM) and novel object recognition task were used to detect the changes of memory behavior before and after transplanting NPC cells in AD model mice; Immunofluorescence, immunohistochemistry and Western-blot were used to detect the differentiation and migration ability of NPCs transplanted into hippocampus. GraphPadPrism 7.0 software was used for statistical analysis using t test. Result In the Morris water maze experiment, the escape latency (14.12 ± 7.45) s before the platform of the mice injected with NPCs and factors was found to be significantly lower than that of the AD model mice injected with PBS [(39.65±4.64) s, F = 2.578, P = 0.0094]. After 24 hours with platform removed, the escape latency of the mice injected with NPCs and factors (15.12±3.52) s was still lower than that of PBS group [(37.17±2.18) s, F = 2.598, P = 0.0003], and the time of factor group (16.62±3.23) s was also lower than that of the PBS group[(37.17±2.18) s, F = 2.186, P = 0.0004)]. In the new object recognition experiment, the NPC + factor group was better (68.46±2.4)% than the PBS group [(54.47±4.79)%, F = 3.983, P = 0.018]. The factor group (65.20±1.03)% was also better than the PBS group [(54.47±4.79)%, F = 21.63, P = 0.042]. Results show that, the memory cognitive function AD mice was improved at an early stage of treatment. Over time, the memory improvement of the NPC group lasted longer. Western blot results showed a decrease in cholinergic neurons in the hippocampus of AD model mice compared with normal C57 mice. After transplantation of NPCs, the number of cholinergic neurons in the brain of AD model increased. Immunofluorescence and immunohistochemistry showed that, the transplanted NPCs survived in the brain and differentiated into cholinergic neurons. Conclusion Factor-incubated NPCs transplanted in bilateral hippocampus of AD model rats improve memory cognitive function of AD rats by differentiating into functional cholinergic neurons. Key words: Alzheimer's disease; NPCs; Fibrin; Cholinergic neurons; Animal models; Cell transplantation