Widzowski D V, Cory-Slechta D A
Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, New York 14642.
Neurotoxicology. 1994 Summer;15(2):295-307.
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.
有人提出,许多因接触铅而产生的行为表现的神经生物学基础,可能是由于特定脑区的选择性易损性,比如海马体,在一些研究中已报道该区域有优先蓄积现象。然而,这些发现并非一成不变,事实上,已发现其会随给药参数而变化。本研究检测了产后大鼠通过食用含0、100、350、1000或2000 ppm醋酸铅溶液的哺乳母鼠接触铅后,铅在脑中的潜在区域蓄积情况。在子代7、14、21、40或60日龄时将其处死,把脑部分解为12个区域,包括纹状体、伏隔核、下丘脑、丘脑、腹侧(被盖)和背侧(顶盖)中脑、海马体、额叶、顶叶/颞叶和枕叶皮质、小脑和脑干,用于区域铅分析。所有脑区的铅蓄积模式总体相似。为350、1000和2000 ppm暴露组测定的区域消除半衰期平均约为20天,且各区域之间无差异。在测定脑铅含量之前,无论脑是否经过灌注,区域脑铅水平并无差异。然而,在计算铅浓度时使用干重而非湿重,以及包括在干燥前浸泡在甲醛中的程序,可能会因不同脑区的液体体积差异而导致脑铅水平出现区域差异。综上所述,这些数据不支持先前关于铅在任何脑区(包括海马体)选择性区域蓄积的发现,至少在产后铅暴露和湿重测量条件下如此。虽然脑区对铅的敏感性可能确实存在差异,但脑区之间反应的任何差异可能应归因于铅与该区域独特或富集的生化或细胞靶点相互作用的差异,而非铅蓄积的差异。