| The effects of low-level lead exposure on learning andmemory in defferent developmental stages in ratsAbstractObjective To study the changes of neuronal behavior, hippocampal long-term potentiation (LTP) and mRNA expression of NMDAR1/NMDAR-2R in rats chronically exposed to low-level lead in different growth stages, and to make sure the high-risk population exposed to lead and hence provide the theoretical basis for the mechanism of its effect on learning and memory.Methods The rat models were established by exposing rats to 0.2% lead acetate solution in different developing stages and divided into control group, lead exposure after ablactation group (Group A), lead exposure during perinatal period group (Group B) and persistent lead exposure group (Group C). The changes of memory ability, LTP, microstructure and the mRNA expression of NMDAR1/NMDAR-2A in the hippocampus were administered by Morris water maze, extracorporeal hippocampal slices method, electron microscopy and in situ hybridization.Results (1) The results of Morris water maze showed that in Group B and Group C, the average escape latency was significantly different from the control group (P<0.05), but there was no significant difference between Group A and the control group (P>0.05). As for cognition ability, the rats in the control group and Group A could distinguish and find rapidly the directions from the third test on. However, the rats in Group B and Group C could not do this, with a significant difference between 2 groups (P<0.0l). (2) In the region CAl of extracorporeal hippocampal slices, LTP detection showed that the blood lead and brain lead in Group A was obviously higher than the control group, yet there appeared no significant LTP injury (P>0.05). The blood lead\ t \, ff,and brain lead leve1s in Group B were near to that in the control group but LTPi11jury haPpelled in both Group B and Group C (P<0.05). (3) From in situhybridization, it was shown that in the developing phase, effect of leadexposure on mRNA expression of NMDAR1/NMDAR-2A maintained specificin the hippocampus and age-dependent, especia1ly in the regions CA1, CA3and dentate gyrus (DG). Compared with the control group, at l6tll day the meanoptical density (OD) of mRNA expression of NMDAR1 in pyramidal cel1 layerof hippocampus in Group C was increased to 18.75% and l3.20% respective1yin the regions CA1 and CA3, but lowered to l4.29% in the DG cell layer; at32tll and 64tll day, no changes were found except fOr a DG decrease of 9.67%,l0.67%. The mRNA expression of NMDAR-2A in various hippocampalregions changed in different developing phases. Compared with the controIgroup, the mean OD in Group B and Group C was decreased; in Group C, at16tll day, CA1 decreased 14.28%, CA2 8.82%, CA3 12.5% and DG 13.51%; at32lh and 64th day, DG was decreased 11.43% and 14.7l% respectively. mRNAexpression changes of NMDARlMMDAR-2A in different regions inhippocampus were approximately similar in Group B and Group C, yet notsignificantly different between Group B and the control group (P>0.05). (4)Electron scopic observation: in the early developing phases, in the region CA l,the changes include myelinic layeY, Golgi complex ectatic vacuole, neuropilevacuole and abnormal dense bodies in cytoplasm and lysosome in theperipheral vessels, pyknotic compact of gliocyte, peripheral interstitia1 edema,disorder of cytoplasmic co1lacin and mitochondrial compact. In fact, nosignificant change occurred in the structure of synapsis.Conclusions (1) In the criticql phase of hippocampal development, thelead exposure can affect the discrimination and LTP amplitude in the regionCA1; furthermore, such effect will last to the grow-ups of rats. The leadexposure after ablactation has little effect on memorization of rats. From above,IlIwe can infer that pregnant women and babies are the high-risk population of lead exposure. (2) The chronic low-level lead exposure may disturb the normal NMDAR mRNA expression... |
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