Tiffany-Castiglioni E, Sierra E M, Wu J N, Rowles T K
Department of Veterinary Anatomy, Texas A&M University, College Station 77843-4458.
Neurotoxicology. 1989 Fall;10(3):417-43.
In this article we evaluate evidence that neuroglia (astroglia and oligodendroglia) are primary targets for lead toxicity in the central nervous system or mediate its pathogenesis. An integrated overview of morphologic and biochemical evidence from clinical cases, experimental animals, and cell culture models is attempted. Our review encompasses both high-level lead exposure that produces lead encephalopathy and low-level lead exposure that is associated with cognitive deficits. We also discuss the selection of toxicologically relevant lead doses for cell culture studies. The evidence is compelling that both astroglia and oligodendroglia respond directly or indirectly to lead exposure in ways that could impair brain function. However, at this time more is understood about the responses of astroglia than those of oligodendroglia. Though oligodendroglia appear sensitive to lead in cell culture, as measured by loss of viability and enzyme activity, it is not clear whether their responses to Pb exposure in vivo are primary or secondary to other tissue and cell damage. Astroglia show a definitive primary response in vivo and in vitro to high-level lead exposure, the uptake and storage of Pb intracellularly, possibly by Pb- binding macromolecules. Astroglia also exhibit reactive gliosis, but probably as a secondary response to other tissue damage by high lead levels. The hypothesis that astroglia serve a protective function in the brain by acting as a lead depot in encephalopathy is well supported by several whole animal and cell culture studies. In addition, alterations of glutamine synthetase activity, which have been reported in the astroglia of animals chronically exposed to low levels of lead, bear further investigation.
在本文中，我们评估了神经胶质细胞（星形胶质细胞和少突胶质细胞）是中枢神经系统铅毒性的主要靶点或介导其发病机制的证据。我们试图对来自临床病例、实验动物和细胞培养模型的形态学和生化证据进行综合概述。我们的综述涵盖了导致铅中毒性脑病的高水平铅暴露以及与认知缺陷相关的低水平铅暴露。我们还讨论了细胞培养研究中毒理学相关铅剂量的选择。有令人信服的证据表明，星形胶质细胞和少突胶质细胞均以可能损害脑功能的方式直接或间接对铅暴露作出反应。然而，目前对星形胶质细胞反应的了解比对少突胶质细胞反应的了解更多。尽管在细胞培养中，少突胶质细胞对铅似乎敏感，可通过活力丧失和酶活性来衡量，但尚不清楚它们在体内对铅暴露的反应是原发性的还是继发于其他组织和细胞损伤。星形胶质细胞在体内和体外对高水平铅暴露均表现出明确的原发性反应，即细胞内摄取和储存铅，可能是通过与铅结合的大分子。星形胶质细胞还表现出反应性胶质增生，但这可能是对高铅水平导致的其他组织损伤的继发反应。星形胶质细胞在脑病中作为铅库发挥保护作用的假说得到了多项整体动物和细胞培养研究的有力支持。此外，长期低水平接触铅的动物星形胶质细胞中谷氨酰胺合成酶活性的改变值得进一步研究。
