Abstract: Objective: To investigate the effects of lead exposure during pregnancy and lactation periods on the learning and memory abilities and the expressions of c-fos and parvalbumin(PV) in hippocampus tissue of the offspring rats, and to clarify the possible mechanism of lead on the memory function impairment during nervous system development. Methods: Eight female Wistar rats during pregnancy period were randomly divided into control group and low,medium and high doses of lead-exposed groups. The rats in low,medium and high doses of lead-exposed groups were given deionized water containing 0.05%, 0.10%, and 0.20% lead acetate, and the rats in control group were given deionized water. Ten days after the pups were born, Morris water maze was used to measure the learning and memory abilities of the offspring rats and atomic absorption spectrometry was used to measure the blood and hippocampal lead concentrations of the offspring rats.Biochemical method was used to determine the nitric oxide (NO) levels and nitric oxide synthase (NOS) activities in hippocampus tissue of the offspring rats in various groups. The expressions of c-fos and PV proteins in hippocampus tissue of the offspring rats in various groups were detected by Western blotting method.Pearson correlation analysis was used to analyze the correlations between the expression levels of c-fos and PV proteins in hippocampus tisue of the offspring rats and the learning indexes,the NO level,and the NOS activity in hippocampus tissue. Results: In the positioning navigation test, compared with control group, the average escape latencies and the swimming distances of the offspring rats in medium and high doses lead-exposed groups were increased(P<0.05); in the space exploration experiment, the time of staying in the target quadrant and the number of crossing platform of the offspring rats in medium and high doses of lead-exposed groups were reduced(P<0.05).The blood lead and hippocampal lead concentrations of the offspring rats in various groups were statistically different (F=176.44,P<0.01;F=37.37,P<0.01); compared with control group, the blood lead and hippocampal lead concentrations of the offspring rats in low,medium and high doses of lead-exposed groups were significantly increased(P<0.05). There were statistical differences in the NO levels and the NOS activities in the hippocampus tissue of the offspring rats in various groups(F=4.105,P<0.05;F=3.443,P<0.05). Compared with control group, the NO level in hippocampus tissue of the offspring rats in high dose of lead-exposed group was significantly reduced(P<0.05), and the NOS activity was decreased (P<0.05).Compared with control group,the expression levels of c-fos protein in hippocampus tissue of the offspring rats in different doses of lead-exposed groups were decreased(P<0.05), and the expression levels of PV protein in hippocampus tissue in medium and high doses of lead-exposed groups were increased (P<0.05).The results of Pearson correlation analysis showed that the expression level of c-fos protein in hippocampus tissue of the offspring rats was positively correlated with the learning ability indexes of the water maze test and the NO level and the NOS activity in the hippocampus tissue (P<0.01); the expression level of the PV protein in hippocampus tissue of the offspring rats was negatively correlated with the learning ability indexes of the water maze test and the NO level and the NOS activity in the hippocampus tissue (P<0.01). Conclusion: Lead exposure during pregnancy and lactation periods can impair the learning and memory abilities of the offsprings rats, and the mechanism is related to the decrease of c-fos protein expression level and the increase of PV protein expression level in the hippocampus tissue.

Key words: lead, hippocampus, learning and memory, c-fos, parvalbumin, pregnancy period, lactation period, offspring rats