Effects Of Low-levels Of Cadmium Exposure In Drinking Water On Learning And Memory Of Offspring And The Possible Mechanisms

Objective: In this research we investigated the influence of dietary exposing to Cd on endocrine, growth and the ability of learning and remembering of offspring mice. By exposing Cd to different period of offspring mice we researched the influence of memory ability on different period; later researches will be conducted to determine the functions of GABAA receptor,thus investigating the relationship between Cd exposing and the function of GABAA receptor.Method: The C57BL/6 mice got diets and water freely and the situation, material were restrained of none Cd pollution strictly. We conducted the pregnant mice into two groups randomly and one group of the two groups above was given normal water,as the other group was feed by water which contains Cd Cl2 10mg/L. After the delivery we reserved 6 offspring mice randomly each couple. After weaning we separated them by gender and gave them same exposing until 12 weeks after delivery(PND 84). We collected the basic information of the offspring mice after delivery and on PND 21,PND 35, PND 49 and PND 84 we executed some mice in order to gather the serum and separated the hippocampus; some mice would conduct Morris water maze experiment on PND 49 which others condect Y maze experiment on PND84. Graphite furnace atomic absorptionspectrometry method were used to detect concentration of cadmium in serum.ELISA(Enzyme-Linked Immuno Sorbent Assay) was used to examine the serm levels of Testosterone and Estradio(E2) in the offspring mice; The histopathologic changes in CA3 field of the hippocampus was observed using HE stain;Immunohistochemistry(IHC) technique was used to detect the expression stastus of GABAa Rα5 and GABAa Rδ. Western blotting were used to observe the expression levels of GABAa Rα5 and GABAa Rδ.Results: The effect of mice exposure to cadmium on body weight, the body length and tail length of the offspring mice wasn’t significant difference at PND1( P>0.05).Compared with the control, the body weight was not significant difference(P>0.05), no matter female and male all the time(PND21 、 PND35 、 PND84).But concentration of cadmium in serum was increased significantly among the offspring mice exposure to cadmium(P < 0.05). On the one hand, the concentrations of Testosterone and Estradio(E2) in serum were not altered significantly among the male. On the other hands, the concentrations of E2 were decreased among the female at PND49(P<0.05).Behavioral experiments showed: in Y maze experiment at PND84, there was no statistically difference of the number of arm visits, the duration of novel visits and the entrances of novel visits among the male. However, compared with the control, the entrances of novel visits and the number of arm visits were decreased among the female(P<0.05). In Morris water maze, the escape latency of development offspring mice was increased significantly(P < 0.05).What’s more, Space exploration experiments showed mice exposure to cadmium had spent less time in target quadrant(P < 0.05) at PND49. The neuropathological changes were characterized by HE stain, decreased neuron number,worse cell morphology in the CA3 field of hippocampus in the female offspring mice at PND84. The expression position of GABAa Rα5 and GABAa Rδ appeared at membrane and we found the expression stastus of GABAa Rδ in cytoplasm by optical microscope using IHC technique. There was significant difference in expression of GABAa Rα5 in hippocampus at PND35 、 PND49 and PND84 and GABAa Rδ in hippocampus at PND84(P<0.05).Conclusion: Low-levels of cadmium exposure cloud disturb the E2 in serum of offsprings, influence the offspring’s growth, cause learning and memory impairment in offspring mice and the mechanism may be that cadmium exposure promotes decrease expression of GABAa Rα5 and GABAa Rδ.