BMSCs transfected with TERT facilitate the restoration of cognition in rats with vascular dementia

WANG Fei; CHANG Guang-ming; GENG Xin

doi:10.3969/j.issn.1002-266X.2014.13.001

Abstract：Objective To study the molecular mechanisms underlying the effects of bone marrow mesenchymal stem cells (BMSCs) transfected with telomerase reverse transcriptase (TERT) on the restoration of learning and memory ability and the impact on synaptic plasticity in the hippocampal CA 1 area of rats with vascular dementia (VD).Methods Rat BMSCs were isolated and identified , then transfected by pLXSN-TERT recombinant .Colony formation assay in soft agar was used to detect the tumorigenicity of TERT-BMSCs in vitro .Thirty-six male Wistar rats were randomly divided into the con-trol group, VD group, BMSCs group and TERT-BMSCs group.Two-vessel occlusion (2VO) was employed to make VD models .Morris water maze test was done for the detection of spatial learning and memory ability .Then the ultrastructures of synapses in the four groups were detected by transmission electron microscope .The expression of BDNF , NMDAR1 and SYN in hippocampal CA 1 region was determined by immunohistochemistry .Results Both Morris water maze test and transmission electron microscope showed that the behavior and morphology were improved in the BMSCs and TERT -BMSCs groups as compared with that of the VD group (all P<0.05), and the TERT-BMSCs group was better (all P<0.05). The average expression levels of BDNF , NMDAR1 and SYN protein in the BMSCs and TERT-BMSCs groups were higher than those in the VD group (all P<0.05), and TERT-BMSCs group had more significant effects than BMSCs group (all P<0.05).Conclusions TERT-BMSCs can more significantly improve the ability of spatial learning and memory in VD rats than regular BMSCs .This mechanism might be associated with enhancement of the expression of BDNF , NMDAR1 and SYN protein in hippocampal CA 1 region and affecting the synaptic plasticity .