Chen H H, Ma T, Hume A S, Ho I K
Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson 39216, USA.
Biomed Environ Sci. 1998 Mar;11(1):61-9.
Chronic low-level lead (Pb) exposure in children is known to cause a deficit in learning and memory. In vitro studies have demonstrated that Pb altered protein kinase C (PKC) activity. Especially, hippocampal PKC has been correlated with performance in several learning tasks. The effects of Pb exposure on hippocampal PKC were investigated during development at various postnatal ages: postnatal day (PN) 7, 14, 28, and 56. Two-tenth % Pb acetate was administered to pregnant and lactating dams and then administered to weanling rats in drinking water. PKC activity was measured in both membrane and cytosolic fractions from the hippocampi of the controls and Pb-exposed animals. Pb-induced increase in PKC activity in the cytosolic fraction was observed in the PN56 rats. In contrast, PKC activity was decreased by Pb at PN7 in the membrane fraction. Furthermore, a significant decrease in the ratio of membrane to cytosolic PKC activity which is representative of PKC distribution was observed in the PN28 and PN56 Pb-exposed rats relative to the same-age controls. This study indicates that chronic Pb exposure during development influences hippocampal PKC activity and distribution. These changes may be involved in the subclinical neurotoxicity of chronic Pb exposure in young children.
已知儿童长期低水平接触铅（Pb）会导致学习和记忆缺陷。体外研究表明，铅会改变蛋白激酶C（PKC）的活性。特别是，海马体中的PKC与多项学习任务的表现相关。在出生后不同年龄段（出生后第7天、14天、28天和56天）的发育过程中，研究了铅暴露对海马体PKC的影响。给怀孕和哺乳期的母鼠喂食0.2%的醋酸铅，然后给断奶大鼠饮用含铅的水。在对照组和铅暴露组动物的海马体中，分别测量膜组分和胞质组分中的PKC活性。在出生后第56天的大鼠中，观察到铅导致胞质组分中的PKC活性增加。相反，在出生后第7天，膜组分中的PKC活性因铅而降低。此外，相对于同龄对照组，在出生后第28天和56天的铅暴露大鼠中，代表PKC分布的膜与胞质PKC活性之比显著降低。这项研究表明，发育过程中的慢性铅暴露会影响海马体PKC的活性和分布。这些变化可能与幼儿慢性铅暴露的亚临床神经毒性有关。
