Homogeneity of regional brain lead concentrations.

Homogeneity of regional brain lead concentrations.
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发表时间:
1994
期刊:
影响因子:
3.4
通讯作者:
D. Widzowski;D. Cory-Slechta
D. Widzowski;D. Cory-Slechta
中科院分区:
医学3区
文献类型:
--
作者:
D. Widzowski;D. Cory-Slechta

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有人提出,由于铅暴露而产生的许多行为表现的神经生物学基础可能是由于特定大脑区域的选择性脆弱性,例如海马体,一些研究报告了该区域的优先积累。然而,这些发现并不是一成不变的,事实上,它们随剂量参数的变化而变化。这项研究检查了大鼠出生后通过食用 0、100、350、1000 或 2000 ppm 醋酸铅溶液的护理母鼠接触铅后大脑中铅的潜在区域积累。在 7、14、21、40 或 60 天时处死后代,将大脑解剖成 12 个区域,包括纹状体、伏核、下丘脑、丘脑、腹侧(被盖)和背侧(顶盖)中脑、海马、额叶、顶叶/颞叶和枕叶皮质、小脑和脑干,以检测区域 Pb分析。所有大脑区域通常都以相似的模式积累铅。针对 350、1000 和 2000 ppm 暴露组确定的区域消除半衰期平均约为 20 天,并且区域之间没有差异。无论在测定脑 Pb 之前是否对大脑进行灌注,区域脑 Pb 水平都没有差异。然而,通过在计算铅浓度时使用干重而不是湿重,以及通过在干燥前浸泡在甲醛中的程序,可以引入大脑铅水平的区域差异,这可能是由于不同大脑区域的液体体积不同造成的。总而言之,这些数据并不支持之前关于铅在任何脑区(包括海马体)选择性区域积累的发现,至少在产后铅暴露和湿重测量的条件下是这样。虽然大脑区域之间对铅的敏感性确实可能存在差异,但大脑区域之间反应的任何差异可能应归因于铅与该区域独特或丰富的生化或细胞靶标相互作用的差异,而不是铅积累的差异。
It has been proposed that the neurobiological basis of many of the behavioral manifestations arising in response to Pb exposure may be due to selective vulnerability of particular brain regions, such as hippocampus, a region in which preferential accumulation has been reported in some studies. However, these findings have not been invariant and, in fact, have been found to vary with dosing parameters. This study examined potential regional accumulation of Pb in brain following postnatal exposure of rats to Pb via nursing dams consuming Pb acetate solutions of 0, 100, 350, 1000, or 2000 ppm. Offspring were sacrificed at 7, 14, 21, 40 or 60 days of age and brains dissected into 12 regions, including striatum, nucleus accumbens, hypothalamus, thalamus, ventral (tegmentum) and dorsal (tectum) midbrain, hippocampus, frontal, parietal/temporal, and occipital cortices, cerebellum and brain stem for regional Pb analyses. All brain regions generally accumulated Pb in a similar pattern. Regional elimination half-lives, determined for the 350, 1000 and 2000 ppm exposure groups, averaged about 20 days and did not vary between regions. Regional brain Pb levels were not different whether brains were perfused or not prior to brain Pb determinations. However, regional differences in brain Pb levels could be introduced by using dry, rather than wet weights in the calculation of Pb concentrations, and by procedures including soaking in formaldehyde prior to drying, probably as a result of the differential fluid volume of different brain regions. Taken together, these data do not support previous findings of selective regional accumulation of Pb in any brain region, including the hippocampus, at least under conditions of postnatal Pb exposure and wet weight measures. While there may indeed be differences among brain regions in sensitivity to Pb, any differences in response among brain regions should probably be ascribed to differences in the interactions of Pb with biochemical or cellular targets unique or enriched in that region rather than to differences in accumulation of Pb.