Reddy Gottipuolu R, Basha Md Riyaz, Devi C Bhuvaneswari, Suresh Ambati, Baker John L, Shafeek Abdul, Heinz Josephine, Chetty Chellu S
Department of Natural Sciences and Mathematics, Savannah State University, P.O. Box 20600, Savannah, GA 31404, USA.
Int J Dev Neurosci. 2003 Oct;21(6):347-52. doi: 10.1016/s0736-5748(03)00071-6.
Exposure to low-levels of lead (Pb) during early development has been implicated in behavioral abnormalities and cognitive deficits in children. The present study is focused on developmental changes in hippocampus and cerebellum of rats following perinatal exposure to Pb. Pregnant rats were exposed to 0.2% Pb-acetate from gestation day 6 (GD 6) through postnatal day (PND) 21 and the activity levels of acetylcholinesterase (AChE) were estimated in cerebellum and hippocampus of pups at specific time points for 5 weeks. In both the brain regions, Pb-exposure decreased AChE activity with an increase in age. Histochemical observations conducted in 35 days old rat brain showed decreased AChE activity conspicuously in stratum oriens and dentate gyrus of hippocampus, and molecular and granule cell layers of cerebellum. In vitro studies conducted in 35 days old rat brain showed a considerable decrease in the specific activity of AChE at high concentrations (50-100 microM) of Pb in a concentration-dependent manner. However, at low concentrations (5-20 microM), Pb failed to produce such changes. In the presence of eserine (physostigmine), the specific inhibitor of AChE, the inhibitory effect of Pb was potentiated and this was more pronounced at low-concentrations of Pb. The behavioral responses in open-field also showed a significant decrease in both Pb exposed as well as eserine administered rats. These data suggest that low-level perinatal Pb-exposure induces alterations in cholinergic system in the cerebellum and hippocampus of developing brain even after the withdrawal of Pb-exposure, that may contribute to behavioral and learning deficits.
在早期发育过程中接触低水平铅（Pb）与儿童行为异常和认知缺陷有关。本研究聚焦于围产期接触铅后大鼠海马体和小脑的发育变化。怀孕大鼠从妊娠第6天（GD 6）至出生后第21天（PND 21）暴露于0.2%醋酸铅，在5周的特定时间点估计幼崽小脑和海马体中乙酰胆碱酯酶（AChE）的活性水平。在这两个脑区，铅暴露均使AChE活性随年龄增长而降低。对35日龄大鼠脑进行的组织化学观察显示，海马体的原层和齿状回以及小脑的分子层和颗粒细胞层中AChE活性明显降低。对35日龄大鼠脑进行的体外研究表明，在高浓度（50 - 100 microM）铅作用下，AChE的比活性以浓度依赖方式显著降低。然而，在低浓度（5 - 20 microM）时，铅未能产生此类变化。在乙酰胆碱酯酶的特异性抑制剂毒扁豆碱存在的情况下，铅的抑制作用增强，且在低浓度铅时更为明显。旷场实验中的行为反应也显示，铅暴露大鼠和给予毒扁豆碱的大鼠均显著下降。这些数据表明，即使在停止铅暴露后，围产期低水平铅暴露仍会导致发育中大脑小脑和海马体胆碱能系统的改变，这可能导致行为和学习缺陷。
