Study And Memory Impairment Induced By Lead In Early Life Of SD Rats And The Protective Effect Of Resveratrol

ObjectiveLead(Pb)exposure in early life can cause irreversible effects on the synaptic plasticity of the hippocampus and eventually lead to learning and memory dysfunction.However,the specific mechanism of its damage has not been clarified.The purpose of this study is to explore the changes of SIRT1 and its related signal pathway molecules expression and the differences of downstream synaptic related proteins regulated by SIRT1 and its related signal pathway molecules in the hippocampus of mice exposed to Pb in early life,to find out the specific mechanism of synaptic plasticity damage caused by Pb exposure.The specific role of resveratrol administration in early life was further studied,which might provide a basis for the prevention and treatment of cognitive dysfunction caused by early-life lead exposure.MethodsSprague-Dawley rats were used to establish a lead exposure model in early life,and male offspring after 21 days of weaning were selected for follow-up experiments.Morris water maze was used to detect the effect of Pb exposure on the spatial learning and memory ability of rats in early life.The blood lead level(BLL)of the rat was detected by graphite furnace atomic absorption spectrometry(GFAAS).The presynaptic proteins Syn-1,LIMK1 and post-synaptic proteins PSD-95,NL-1 mRNA regulation trends were controlled by RT-qPCR,and the protein expression of these target genes was detected by Western blot.Results1.Effects of Pb exposure in early life on spatial learning and memory of ratsThe results of the water maze show that compared with the control group,the incubation period of the 0.2%Pb-exposed rat in the positioning and navigation experiment was significantly prolonged(P<0.05),and in the experiment of space exploration,the time of the first time on the platform increased significantly(P<0.01),and the times of crossing the platform and the percentage of staying time in the target quadrant decreased significantly(P<0.01;P<0.001 respectively).Besides,compared with the 0.05%Pb-exposed group,the escape latency of the 0.2%Pb-exposed group was prolonged(P<0.05),and the number of crossing platforms and the percentage of stay in the target quadrant were also significantly reduced(P<0.05;P<0.01 respectively).Compared with the 0.2%Pb-exposed,the escape latency and the time before the first stage of rat in the 0.2%Pb+Res group were significantly shortened(P<0.05;P<0.05 respectively),and the times of crossing platform and the percentage of staying time in the target quadrant were significantly increased(P<0.05;P<0.05 respectively).2.Determination of blood lead level by GFAASCompared with the control group,the BLL of the three groups with different concentrations of Pb exposure increased significantly(P0.05%vs cont<0.001;P0.1%vs cont<0.001;P0.2%vs cont<0.001 respectively),and the increase trend was positively correlated with the concentration of Pb exposure(P0.1%VS 0.05%<0.001;P0.2%vs 0.05%<0.001;P0.2%vs 0.1%<0.001 respectively).Compared with the 0.2%Pb-exposed group,the BLL of the 0.2%Pb-exposed+Res group and the 0.2%Pb-exposed+EDTA group were significantly reduced(P<0.001;P<0.001 respectively),but still higher than the control group(P<0.001;P<0.01 respectively).3.Expression of target gene mRNA in rat hippocampus by Pb exposureThe mRNA expression levels of SIRT1,CREB,BDNF,Syn-1,LIMK1,PSD-95,NL-1 by RT-qPCR assay in 0.2%Pb-exposed group were significantly lower than those in the control group and 0.05%Pb-exposed group,and the differences were statistically significant.In addition,compared with the 0.1%Pb-exposed group,the expression levels of SIRT1,Syn-1,LIMK1,PSD-95 and NL-1 in the 0.2%Pb-exposed group were also significantly reduced(P<0.05;P<0.01 respectively).The mRNA expression levels of SIRT1,CREB,BDNF,Syn-1,LIMK1,PSD-95,and NL-1 in the 0.2%Pb+Res group were significantly increased compared with the 0.2%Pb-exposed group,and the differences were statistically significant.4.Expression level of target gene protein in rat hippocampus tissuesThe protein expression levels of SIRT1,CREB,BDNF,Syn-1,LIMK1,PSD-95,NL-1 by Western blot assay in 0.2%Pb-exposed group were lower than those in the control group and 0.05%Pb-exposed group,and the difference was statistically significant.Compared with 0.2%Pb-exposed group,SIRT1,p-CREB,BDNF,Syn-1,LIMK1,PSD-95,NL-1 protein expression levels in 0.2%Pb+Res group were significantly up-regulated respectively.In three different concentrations of Pb,the Pro-BDNF protein level increased significantly with the increase of Pb concentration,and Res could weaken its up-regulation due to Pb exposure(P<0.001).Conclusions1.Synaptic lesions of rats exposed to Pb in early life is related to the decreased expression of SIRT1/CREB/BDNF signaling molecules and its associated cascade pre-and post-synaptic proteins.2.Resveratrol can improve the expression of pre-and post-synaptic proteins by activating the SIRT1/CREB/BDNF signaling pathway,thereby improving learning and memory impairment caused by Pb exposure.