Effects of ginkgo biloba extract on learning and memory and protection of hippocampal neurons in rats with vascular dementia

Abstract

Objective To investigate the effects of ginkgo biloba extracts (EGb761) on learning and memory and the protective effect on hippocampal neurons in rats with vascular dementia (VD). Methods Ninety rats were randomly divided into sham-operated group, model group and EGb761-treated group, with 30 rats in each group. Rats in each group were examined at 15 days, 1 month and 2 months, with 10 rats in each time point. VD model was established by bilateral carotid artery occlusion combinding with injection of sodium nitroprusside. Morris water maze test was used to detect the learning and memory function of rats. The expression of glial fibrillary acidic protein (GFAP) was observed by immunofluorescence. Western-blot was used to detect the protein expression of P-glycoprotein (P-GP), excitatory amino acid transporters 2(EAAT2), caspase-3 and cleaved caspase-3.RT-PCR was used to detect the mRNA expression of P-GP and EAAT2 in the hippocampus of rats in each group. Results Compared with sham-operated group, the escape latency (EL) was significantly prolonged at each time point in model group (sham-operated group: 15 days(15.52±3.23)s, 1 month(14.21±2.62)s, 2 months(15.37±1.66)s; model group: 15 days(30.35±2.30)s, 1 month(40.78±3.55)s, 2 months(33.88±1.47)s; all P<0.01). The EL of EGb761-treated group was significantly shorter than that of the model group(EGb761-treated group: 15 days(25.69±2.44)s, 1 month(20.78±1.72)s, 2 months(18.23±1.67)s, all P<0.01). Immunofluorescence showed that the expression of GFAP in EGb761-treated group was lower than that of the model group (P<0.01). Western blot showed that cleaved caspase-3 protein expression in EGb761-treated group at each time point was significantly lower than that in the model group (P<0.01). Western-blot and RT-PCR results showed that the protein and mRNA expression of P-GP and EAAT2 in EGb761-treated group at 15 day and 1 month time points were significant increased than those in the model group (P<0.01). At 2 month time point, which were lower than those in the model group (P<0.01). Conclusion EGb761 can improve the learning and memory ability of VD rats, and regulate the protein and mRNA expression of P-GP and EAAT2 in hippocampus of VD rats at different time points (up-regulated in 1 month and down-regulated in 2 month), and down-regulate the expression of cleaved caspase-3 and GFAP at different time points, thereby delaying the brain damage of VD rats and protecting neurons. Key words: Ginkgo biloba extracts; Vascular dementia rats; P-glycoprotein; Excitatory amino acid transporters 2; Glial fibrillary acidic protein