Zheng W, Shen H, Blaner W S, Zhao Q, Ren X, Graziano J H
Division of Environmental Health Sciences, School of Public Health, New York, New York, USA.
Toxicol Appl Pharmacol. 1996 Aug;139(2):445-50. doi: 10.1006/taap.1996.0186.
The choroid plexus, which is responsible for the maintenance of the biochemical milieu of the cerebrospinal fluid (CSF), avidly sequesters Pb. In order to test the hypothesis that chronic Pb exposure may impair choroid plexus function, male weanling Sprague-Dawley rats were exposed to Pb in drinking water at doses of 0, 50, or 250 micrograms Pb/ml (as Pb acetate) for 30, 60, or 90 days. The function of the choroid plexus was assessed as reflected by CSF concentrations of transthyretin (TTR, a major CSF protein manufactured by brain choroid plexus) and CSF essential metal ions (Ca2+, Mg2+, K+, and Na+). TTR concentrations were determined by radioimmunoassay using a monospecific rabbit anti-rat TTR polyclonal antibody, and CSF metal ions analyzed by flame atomic absorption spectrophotometry. Two-way ANOVA of CSF TTR concentrations revealed highly significant dose (p < 0.0001), time (p < 0.0223), and dose-by-time effects (p < 0.0379). Moreover, the percentage of reduction of CSF TTR was directly correlated with Pb concentrations in the choroid plexus (r = 0.703, p < 0.05). Pb exposure significantly increased CSF concentrations of Mg2+, but did not markedly altered CSF concentrations of Ca2+, K+, and Na+. Histopathologic examination under the light microscope did not show distinct alterations of plexus structure in Pb-treated rats. Since TTR is responsible for transport of thyroid hormones to the developing brain, we postulate that the depression of choroid plexus TTR production (and/or secretion) by Pb may impair brain development in young animals by depriving the CNS of thyroid hormones.
脉络丛负责维持脑脊液（CSF）的生化环境，它能大量蓄积铅。为了验证慢性铅暴露可能损害脉络丛功能这一假说，将雄性断乳的斯普拉格-道利大鼠暴露于含0、50或250微克铅/毫升（以醋酸铅形式）的饮用水中30、60或90天。通过脑脊液中转甲状腺素蛋白（TTR，一种由脑脉络丛产生的主要脑脊液蛋白）的浓度以及脑脊液中必需金属离子（Ca2+、Mg2+、K+和Na+）来评估脉络丛的功能。使用单特异性兔抗大鼠TTR多克隆抗体通过放射免疫测定法测定TTR浓度，并用火焰原子吸收分光光度法分析脑脊液金属离子。对脑脊液TTR浓度进行双向方差分析显示，剂量（p < 0.0001）、时间（p < 0.0223）以及剂量与时间的交互作用（p < 0.0379）均具有高度显著性。此外，脑脊液TTR降低百分比与脉络丛中的铅浓度直接相关（r = 0.703，p < 0.05）。铅暴露显著增加了脑脊液中Mg2+的浓度，但未明显改变脑脊液中Ca2+、K+和Na+的浓度。光学显微镜下的组织病理学检查未显示铅处理大鼠的脉络丛结构有明显改变。由于TTR负责将甲状腺激素转运至发育中的大脑，我们推测铅导致脉络丛TTR产生（和/或分泌）减少可能会使中枢神经系统缺乏甲状腺激素，从而损害幼龄动物的脑发育。
