The Protective Role Of Resveratrol On Learning And Memory Damage Of Pubescent Mice By Developmental Exposure To Lead

ObjectiveLead(pb)could induce widespread neurotoxicity and has been reported to be a potential risk factor for cognition.Resveratrol,a natural polyphenol with crucial anti-oxidative property,is recently implicated in preventing cognitive deficits in normal aging and neurodegenerative disorders.The aim of this work is to investigate the possible linkage between Pb exposure during the early life period and the chronic access to resveratrol on spatial learning and memory abilities.MethodsMorris water maze(MWM)test was used to assess spatial learning and memory abilities of C57BL/6 mice which were exposed to Pb about 3 months after lactation,and were divided into six groups in different life point(4-month,13-month and 16-month).The lead content of mice blood was examined by polarography.the expression levels of APP and BDNF mRNA in hippocampus,were detected by Real-time Quantitative PCR(qPCR),and BDNF protein expression was adopted by western blotting.In addition,after exposed to lead for 3 months,the mice were gavaged with Res for another 12 months every other day,and the control group was administered with the same volume of CMC-Na.There were 4 groups in all,control group(Cont),Pb(Ac)2 exposed group(Pb),Pb(Ac)2+ Resveratrol group(PbR),Control + Resveratrol group(CR).The lead content of mice blood was determined.In hippocampus,the expression level of BDNF and SIRT1 mRNA were detected by qPCR,and BDNF,SIRT1 and PGC-1? protein expression were used western blot.ResultsIn the first part,the MWM results showed that,compared to the corresponding control groups,the frequencies to cross the non-exit platform(P<0.05)and the time spent in target quadrant were reduced in the Pb groups(P<0.01).And the first-time duration to cross the non-exit platform was prolonged in the Pb groups(P<0.05).To the blood lead,compared to the corresponding control group,the blood lead level was higher than in the Pb groups.However,to the Pb groups,the blood lead level of the 16-month mice was lower than the other two groups(P<0.001).Concerning the APP mRNA,the 16-month Pb group had a higher level than the control group(P<0.05).About BDNF mRNA,the 13-month Pb group had a higher level than the control group(P<0.05).Then to the protein of BDNF,as the mice got older,the level of proBDNF was increased,but the level of mature BDNF(mBDNF)was reduced.Interestingly(P<0.05),after lead exposure,the level of proBDNF was increased,but the mBDNF was reduced(P<0.01).In the experiment of intervening with resveratrol,the MWM results showed that,compared to the Cont,the first-time duration to cross the non-exit platform was prolonged in Pb(P<0.01),and the time spent in target quadrant was reduced in Pb(P<0.001).But compared to the Pb group,the first-time duration to cross the non-exit platform was reduced and the time spent in target quadrant was increased in Pb(P<0.05).To the mBDNF,in protein,compared to the Cont,the level was reduced in Pb;compared to the Pb,the level was enhanced in PbR.And regarding to mRNA,compared to the Cont,the level was reduced in Pb(P<0.05)but was increased in CR;compared to the Pb,the level was increased in PbR group(P<0.05).Concerning the 8-OHdG in brain,after Pb exposure,there were significant increases in the 8-OHdG content in the cortex(P<0.05)as well as CA1 and CA3(P<0.001).Treatment with resveratrol partly depressed the enhancement of 8-OHdG content in cortex(P<0.05),CA1 and CA3(P<0.001).With regard to the SIRT1,in nucleus of hippocampus and the rate of SIRT1 level in nucleus/cytosol,compared to the Cont,the level was reduced in Pb and PbR(P<0.001);compared to the Pb,the level was increased in PbR(P<0.05).To the SIRT1 mRNA,compared to the Cont,the level was increased in CR(P<0.001).Then about the phosphorylated SIRT1,compared to the Cont,the level was reduced in Pb and PbR;compared to the Pb,the level was increased in PbR(P<0.05).To the PGC-1?,compared to the Cont,the level was reduced in Pb;compared to the Pb,the level was increased in PbR(P<0.05).Conclusions1.Chronic lead exposure on mice in development stage may have a long-term effect on learning and memory ability.2.Resveratrol had protection to learning-memory dysfunction and oxidative DNA damage induced by chronic lead exposure by activating the SIRT1/PGC-1? pathway.