| ObjectiveLead (Pb2+) is a neurotoxicant which is ubiquitous in the environment.Lead can lead to irreversible damages on many functions of nervous system,including decrements in IQ,decreased hearing and vision,and impaired peripheral nerve function, the most principal is its effects on individual intelligence development and learning and memory function.Researchers have shown that the developmental nervous system is more vulnerable to lead toxicity.Lower and lower lead levels were recognized as causing impairment on learning and memory,and the extent of impairment is positive correlation with the contents of lead in blood.No evident low limit exposed threshold has yet been found for the effects of lead on the nervous system during foetal period. In recent years,the researchs on lead toxicity have made some advancements.However, the exact mechanism of impairment on learning and memory is still unclear,so it is significant to research the correlative mechanisms.In the present study,the rat's models of chronic low-level lead exposure at developmental stages were built through feeding dam rats with lead acetate solution from the beginning of pregnancy. We had observed the changes of protein expression of GDNF in hippocampus at different developmental stages and learning and memory at adult stage to explore the mechanisms of lead effect on learning and memory and to provide a theoretical basis for the prevention and therapy of lead poisoning of children.MethodsAdult female Wistar rats (n=30) were used in the present study.After one week normal feeding for accommodation,the femal rats were randomly and equally divided into three groups:control group,0.05% lead acetate (PbAc) and 0.2% lead acetate groups.The female:male for natural mating was 1:1 and the female rats were designated as gestation day 0 (Go) when vaginal plug were observed in the next morning.The pregnant rats were fed with doubly distilled water in control group and 0.05%,0.2% PbAc solution in treatment groups via drinking water from the first day of gestation(G1) until the 21th postnatal day(PN21) of the offspring.After weaning at PN21, the offspring were directly fed with drinking water as their dams until PN28.Western blotting was used to observe the protein expression of GDNF in hippocampus of rats'offspring at PN1,PN3,PN7,PN14,PN2,PN28 and immunohistochemistry was used at PN3,PN7,PN14,PN2,PN28 respectively. The 8 offspring of each group were rest to observe the change of learning and memory using the Morris water maze test at PN56.The contents of lead in blood and hippocamous were determined by atomic absorption spectrophotometer at PN28.Results1.Effect of chronic low-level lead exposure on the contents of lead in blood and hippocamous in rats at the developmental stageCompared to control group,the contents of lead in blood and hippocamous in the lead exposed groups were significantly higher,and the extent of increasing was positive correlation with the concentration of lead in drinking water,and there was statistical difference (P<0.01)。2.Effect of chronic low-level lead exposure on spatial learning and memory in rats at the developmental stageIn the Morris water maze test,the results indicated that lead exposure significantly impaired learning and memory ability (P<0.05,P<0.01),and the extent of impairment was positive correlation with the concentration of lead in drinking water.3. Effect of chronic low-level lead exposure on protein expression of GDNF in hippocampus in rats at the developmental stage(1).In the result of immunohistochemistry:Compared to control group,the protein expression of GDNF in CA1,CA3 regions and dentate gyrus(DG)of hippocampus in the lead exposed groups were significantly decreased at PN3,PN7,PN14,PN21 and PN28,and there was statistical difference (P<0.05,P<0.01),and this exhibited a developmental expressed differences manner.(2).In the result of western blotting:Compared to control group, the protein expression of GDNF in hippocampus in the lead exposed groups showed a decreased tendency at PN1,PN3,PN7,PN14,PN21,PN28, and there was statistical difference (P<0.05,P<0.01) except the 0.05% PbAc group at PNl,and this exhibited a dose-dependent and developmental expressed differences manner.Conclusion1.Chronic low-level lead exposure could significantly impaire learning and memory ability in rats at the developmental stage.2.Chronic low-level lead exposure could decrease the protein expression of GDNF in hippocampus in rats at the developmental stage.In summary,our results demonstrated that chronic low-level lead exposure at the developmental stage could make an impairment on learning and memory and affect the protein expression of GDNF in hippocampus.The changes were likely to signify that GDNF might participate in the process of lead-induced impairement on learning and memory.
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