Experimental research on the effect of lateral ventricle transplantation of neurotrophic factor-transfected cells derived from Glia cell line on vascular dementia in rats

Abstract

Objective To investigate the effect of lateral ventricle transplantation of neurotrophic factor-transfected cells derived from Glia cell line on vascular dementia in rats and gene expression of Drebrin in hippocampal region. Methods By using gene clone technique, the GDNF gene was transfected into SH-SY5Y cell lines. 104 adult male Sprague-Dawley rats weighing (200±20) gram were divided into groups: transplanted group, injected group, control group, all of which accepted operation by permanent ligation of left common carotid artery and clipping right common carotid artery repeatedly to build up model of vascular dementia, and sham operation group which accepted no ligation or clipping. 6 rats from each group were decapitated on the third day, seventh day and tenth day after transplanting treatment were for fluorescence detection. The rest 20 rats in each group were used to detect learning and memory functions by Morris water maze on the third day and decapitated on the fourth day after transplanting treatment. Then GDNF level in temporal lobe were detected by enzyme-linked immunosorbent assay (ELISA), while Drebrin mRNA and protein levels in hippocampal region were detected by real time-PCR and Westernblot respectively. Results There was strong fluorescent light detected around lateral ventricle of rats in transplanted group on the third day after transplantation, which faded on the seventh day and disappeared on the tenth day. The learning and memory functions of rats in transplanted group were improved significantly. The escape latency was shorter in transplanted group than in injected group and control group〔(34.89±4.15) s vs. (43.86±6.95) s, (50.89±3.66) s, both P<0.05〕, while shuttle times through the third quadrant were more often in transplanted group than in injected group and control group〔(11.00±1.49) vs. (9.26±1.38), (8.04±1.12), both P<0.05〕. GDNF level and Drebrin mRNA and protein levels were higher in transplanted group than in injected group and control group〔GDNF: (315.71±27.43) vs. (256.26±19.90), (141.95±21.33), Drebrin mRNA: (5.54±0.35) vs. (3.10±0.33), (1.32±0.23), Drebrin protein: (0.55±0.05) vs. (0.43±0.06), (0.26±0.06), all P<0.05〕. Conclusions GDNF-transfected cells could survive in the lateral cerebral ventricle of rats for about seven days. The method for treating vascular dementia through the technique of transplanting GDNF-transfected cells is certain feasible, which has a better therapeutic effect than GDNF-injection directly into lateral cerebral ventricle. The therapeutic effect of GDNF on vascular dementia may be related to its action of regulating neural plasticity. Key words: Glial cell line-derived neurotrophic factor; Dementia, vascular; Trans-plantation