Microglial responsiveness as a sensitive marker for trimethyltin (TMT) neurotoxicity

Microglial responsiveness as a sensitive marker for trimethyltin (TMT) neurotoxicity

Activation of microglia is a well-documented phenomenon associated with diverse pathological conditions of the central nervous system. In order to investigate the involvement of microglial cells in the neurotoxic action of the heavy metal compound trimethyltin, three-dimensional brain cell cultures...

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Bibliographic Details
Published in:Brain research Vol. 690; no. 1; pp. 8 - 14
Main Authors: Monnet-Tschudi, Florianne, Zurich, Marie-Gabrielle, Pithon, Eric, van Melle, Guy, Honegger, Paul
Format: Journal Article
Language:English
Published: London Elsevier B.V 28-08-1995
Amsterdam Elsevier
New York, NY
Subjects:
Aggregating brain cell culture
Animals
Biological and medical sciences
Biomarkers - chemistry
Cell Differentiation - drug effects
Cells, Cultured
Cellular Senescence - drug effects
Chemical and industrial products toxicology. Toxic occupational diseases
Early development
GAP-43
GAP-43 Protein
Medical sciences
Membrane Glycoproteins - analysis
Metals and various inorganic compounds
Microglia
Microglia - drug effects
Nerve Tissue Proteins - analysis
Neurotoxicity
Rats
Sensitivity and Specificity
Synapsin I
Synaptophysin
Telencephalon - cytology
Telencephalon - drug effects
Telencephalon - embryology
Toxicology
Trimethyltin (TMT)
Trimethyltin Compounds - toxicity
Aggregating brain cell culture
Synapsin I
Synaptophysin
Neurotoxicity
Trimethyltin (TMT)
GAP-43
Early development
Microglia
Rat
Toxicity
Neuroglia
Rodentia
Central nervous system
In vitro
Heavy metal
Vertebrata
Mammalia
Animal
Tin Organic compounds
Brain (vertebrata)
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Summary:Activation of microglia is a well-documented phenomenon associated with diverse pathological conditions of the central nervous system. In order to investigate the involvement of microglial cells in the neurotoxic action of the heavy metal compound trimethyltin, three-dimensional brain cell cultures were treated during an early developmental period, using concentrations at or below the limit of cytotoxicity. Microglial cells were studied by cytochemical staining, using horseradish peroxidase-conjugated B4 isolectin (GSI-B4). In parallel, neurotoxic effects were assessed by determining the content of synaptophysin and synapsin I, both in the total homogenates and in the synaptosomal fraction of the cultures. Changes in the content of the specific growth cone protein, GAP-43, were also analyzed. It was found that low, non-cytotoxic concentrations of TMT (10 −9 to 10 −8 M) caused a significant increase in the number and/or the clustering of microglial cells. A decrease in the synaptic protein (synapsin I, synaptophysin) content was detected at 10 −8 M of TMT in synaptosomal fractions, whereas in the total homogenates, changes in synaptic proteins and GAP-43 were observed only at the cytotoxic TMT concentration (10 −6 M). Although it remains to be shown whether the microglial response is caused by direct or indirect action of TMT, the present findings show that microglial responsiveness can be detected prior to any sign of neuronal degeneration, and may serve as a sensitive indicator for heavy metal neurotoxicity in the brain.
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ISSN:0006-8993
1872-6240
DOI:10.1016/0006-8993(95)00509-O