| Objective: Elevated blood lead level and iron deficiency often coincide in thedevelopment stage when exposed to environmental lead, both of them haveneurotoxicity which induced behavioral and cognitive impariment. Lead and iron areboth absorbed by the same intestinal mechanism. However, the interaction betweenlead exposure and Fe status has been focused on but not been elucidated. Therefore,we established long-term lead exposure rat model to examine the effect of leadexposure on the temporal and spatial variation of brain iron as well as divalentmetal-ion transpoter1and ferroportin1(DMT1/FP1) expression.Methods: Nine weeks sexually mature females were randomly assigned to thedifferent exposure groups, and drank distilled water containing either0,800mg/l or1500mg/l lead acetate for10days. Then, the females were mated with the males(2:1), continued to exposure during gestation and lactation until rat pups beingweaned. At the weaning, male pups corresponding to their mother were divided intocontrol, low lead group(LLG) and high lead group(HLG), and treated with0,300mg/l and900mg/l lead acetate in drinking water. Research were conducted atweaning(PNW3), mid-age(PNW41) and old-age(PNW70). Using inductivelycoupled plasma atomic emission spectroscopy (ICP-AES) to detect blood, cortex andhippocampus lead and iron content, Using Perl’s staining to observe ferric iron in thecortex and hippocampus, Using magnetic resonance imaging(MRI) in vivo toexamine iron accumulation in cortex and hippocampus, Using real-time quantitativePCR(qRT-PCR), western blot and immunohistochemistry(IHC) to detect the mRNAand protein level of DMT1/FP1in cortex and hippocampus.Results:1. Prenatal lead exposure didn’t affect female conception and birthlitter size, but male pups mortality during gestation was obviously increased, themale pups mortality of HLG was significantly higher than the control(P<0.01).Prenatal lead exposure didn’t affect rats’ body weight, there were no differencebetween three groups.2. Lead exposure induced brain iron content increase. ICP-AES showed that iron content in cortex elevated in a dose-dependent manner at weaning, mid-age andold-age. Iron content in hippocampus elevated in a dose-dependent manner in agedrat brain. Perl’s staining found, no or very little staining of ferric iron was observedin the cortex and hippocampus at weaning. At mid age, there was ferric iron in thecortex but no difference among three groups, the ferric iron in the CA3region ofhippocampus increased in a dose-dependent manner with lead exposure. However, adramatic increase in ferric iron staining was observed in the temporal area of cortexand the CA3region of hippocampus in the old-aged brain. MRI examination of theold-aged rat brain indicated that iron was accumulated in the cortex andhippocampus, the lead exposure groups were more than that of control (P<0.05).3. Lead exposure influenced FP1level. The qRT-PCR analysis showed that theFP1mRNA level only decreased in the cortex of mid-aged rat brain and thehippocampus of old-aged rat brain. No differences were found in other age periods.Western blot found, the FP1protein level was down-regulated in the cortex andhippocampus at weaning, mid-age and old-age, the lead exposure groups were lowerthan the control(P<0.05). IHC manifested that FP1protein was down-regulated inthe temporal and parietal area of cortex as well as in CA1/CA3/DG regions ofhippocampus at weaning and old-age (P<0.05).4. Lead exposure influenced DMT1level. The qRT-PCR analysis showed thatthe DMT1mRNA level only decreased in the cortex and hippocampus of theold-aged rat brain. No differences were found in other age periods. Both western blotand IHC found, DMT1protein level of lead exposure groups were higher than thatof control (P<0.05) at weaning, but lower than control at old-age (P<0.05).Conclusion:1. The long-term chronic lead exposure increased the cortex ironcontent in the rat’s brain at weaning but didn’t induce iron overlod, while the DMT1expression increased and the FP1expression decreased. In mid-aged rat brain,chronic lead exposure increased the cortex iron content but without iron overload,besides, caused iron overload in the CA3region of hippocampus, while both DMT1and FP1expression decreased. In old-aged rat brain, chronic lead exposure bothincreased the cortex and hippocampus iron content, and caused iron overload in thetemporal of the cortex as well as in the CA3region of the hippocampus, while both DMT1and FP1expression decreased.Inmay be associated with decreasingexpression of FP1at transcriptional and/or posttranscriptional levels.2. The effect of chronic lead exposure on brain iron might be not subjected toDMT1mediating, but was probably associated with the decrease expression of FP1attranscriptional and (or) post-transcriptional levels. |
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