Effects Of EGCG On Spatial Learning And Memory Ability And Expression Of RAGE Protein In Hippocampus Of Lead Exposuremice

ObjectivesThe purpose of the present study was to investigate the protective effects of EGCG in mice Alzheimer’s disease（AD）-like amyloidosis caused by lead exposure. The parameters observed included spatial learning and memory ability, hippocampal antioxidant enzyme（SOD and GSH-PX） activities and malondialdehyde（MDA） levels, the expression of RAGE protein and contents of Aβ_1-40, Aβ_1-42 protein in hippocampus. It also explored the potential neurological protective mechanism of EGCG in mice AD-like amyloidosis caused by lead exposure by analyzing these parameters. MethodsFifity C57BL/6 aged 3 weeks male mice were assigned to five groups: control group（10 mice）, lead exposed group, low（Pb+1.5mg/kg EGCG）, middle（Pb+1.5mg/kg EGCG）, high（Pb+1.5mg/kg EGCG） dose EGCG intervention groups. Control group was provided with deionized water; Pb exposed group and intervention groups were provided with 0.2% lead containing water. After 8 weeks, low, middle, high dose intervention groups were intragastric administration with EGCG; control group and Pb exposed group were administered with same volume saline. After 4 weeks, the spatial learning and memory ability was evaluated by morris water maze（MWM）. One day after MWM, under anaesthesia condition, the mice blood was drawn from orbital sinus. Their brains were peeled, and hippocampus tissues were separateded on ice. Lead contents in blood were determined by atomic absorption spectrometry; SOD and GSH-PX activity levels and MDA level in hippocampus were measured by corresponding kits. The expression of RAGE protein was measured by Western Blot; Aβ_1-40, Aβ_1-42 contents in hippocampal tissue were determined by correlative ELISA kits. ResultsThe weights of mice: the weights of Pb exposed group and different dose intervention groups were lower than control group（P<0.05） at seven and eleven weeks; middle, high dose EGCG interfering groups were higher than Pb exposed group at 15 weeks（P<0.05）.Reuslts of MWM: the average escape latency in Pb exposed group was great longer than in control group（P<0.05）; compared with Pb exposed group, middle, high dose EGCG interfering groups showed shorter escape latency（P<0.05）. On the 6th day, the times of platform crossings of Pb exposed group were markedly less than control group（P<0.05）; middle, high dose EGCG interfering groups had higher frequency of platform crossings than Pb exposed group（P<0.05）.Blood lead levels: A significant increase in blood lead levels were observed in Pb exposed group and interfering groups compared with control group（P<0.05）.There were no differences in interfering groups（P>0.05）.Activities of hippocampal antioxidant enzymes: the hippocampal SOD and GSH-PX activity levels were significantly decreased in Pb exposed group compared with control group, and the MDA level were significantly increased（P<0.05）. The activity levels of SOD and GSH-PX were higher in middle, high interfering groups than those in Pb exposed group, while the contents of MDA were much lower（P<0.05）.The results of Western blot showed that: the expression of RAGE protein in Pb exposed group was significantly enhanced than that in control group（P<0.05）; compared with Pb exposed group, low, middle, high dose EGCG interfering groups were much lower（P<0.05）.Aβ_1-40, Aβ_1-42 contents: Aβ_1-40, Aβ_1-42 contents in Pb exposed group were significantly higher than those in control group（P<0.05）; midlle, high dose EGCG interfering groups were much lower compared with lead exposed group（P<0.05）. Conclusion（1）Lead exposure can significantly elevate blood lead levels, decrease the mice body weights, and damage the ability of spatial learning and memory. Lead exposure can also cause oxidative stress, increase the expression of RAGE protein and result in a significant accumulation of Aβ in hippocampus.（2）EGCG can improve the the performance of rats in the spatial learning and memory ability and inhibit the produce of Aβ_1-40, Aβ_1-42 in hippocampus. The neuroprotective effect of EGCG is likely to improve the activities of antioxidant en-zyme and decrease the expression of RGAE protein stimulating anti-oxidation mechanism on mice AD-like amyloidosis caused by lead exposure.