The Effect Of Transplantation Of Fibroblasts Modified With Gene NT-4 Into Brain Of AD Rats On Electrophysiology And Behavior

Objective: To observe the effect of transplantation of the fibroblasts modified with gene of NT-4 in hippocampus of AD rats on the behavior, morphology and electrophysiology after transplantation.Methods: 24 SD rats were randomly divided into four groups: sham operation group, AD model group, AD model+fibroblasts transplantation groups, AD model+NT4-fibroblasts transplantation group. AD models were made by transecting bilateral fimbria-fornix. On the tenth day after surgery, the fibroblasts and NT4-fibroblasts were respectively transplanted into the hippocampus of AD rats. Two months after transplantation, the behavior test and electrophysiology test were carried out respectively. The rats were sacrificed and brain tissues were taken out and the NT-4 expression by transplanted NT-4 fibroblasts and choline acetyltransferase (ChAT) expression by host hippocampal cholinergic neurons were tested.Results: Behavior tests show that the average of escapelaterncy of NT-4-fibroblasts transplantation group significantly shortened compared with AD model group (P< 0．01) .Electrophysiology test showed the amplitude of C-P50 in NT-4-fibroblasts transplantation group heigntened significantly than that of AD model group. The restraining if T-P50 significantly strengthened than that of AD model group. And T/C ratio significantly decreased in NT-4-fibroblasts transplantation group than that of AD model group. (P <0．01) .The difference value of S1-S2 amplitude was significantly larger in NT-4-fibroblasts transplantation group than that of AD model group (P< 0．01 ) .Transplanted fibroblasts steadily expressed NT-4 proteins. Immunohistochemistry showed the count of cholinergic neurons significantly increased than that of control group (P<0．01) .Conclusions: Transplantation of NT-4-fibroblasts had provided a long-term and steady expression of NT-4．They can promote the significant recover of behavior, physiologic function and histology of AD rats via NT-4 releasing. This study had provided a good experimental gist and method for application of NT-4 for the therapy of AD.