Lead toxicity in neuroglia.
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.
Tiffany-Castiglioni
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Department of Veterinary Anatomy, Texas A&M University, College Station 77843-4458.
Sierra
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EM
Wu
J N
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Rowles
T K
TK
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology; D005260:Female; D006801:Humans; D007855:Lead Poisoning / Q000503:physiopathology*; D009457:Neuroglia / Q000187:drug effects / Q000502:physiology*; D009836:Oligodendroglia / Q000187:drug effects / Q000502:physiology; D011247:Pregnancy