Neurotypic and gliotypic proteins as biochemical markers of neurotoxicity.
Cells of the central and peripheral nervous system are differentially sensitive to toxic insults. Because biochemical differences between nervous system cell types are revealed by region- and cell-type-specific proteins, we proposed that these unique neuronal (neurotypic) and glial (gliotypic) proteins may be used to detect and characterize the cellular responses to chemical-induced injury (28). We are testing this hypothesis by administering known and suspected neurotoxicants to the developing and mature rat and assessing the effects of these agents on previously characterized neurotypic and gliotypic proteins. Using radioimmunoassays of these proteins in combination with their localization by immunohistochemistry, we have characterized several features of the neurotoxic state: 1) region-dependent patterns of neurotoxicity are revealed by changes in neurotypic and gliotypic proteins; 2) these changes are time-dependent and vary depending on the nature of the insult; and 3) significant changes in neurotypic and gliotypic proteins can be observed where there is no apparent pathology. Data obtained using a number of known neurotoxicants are presented to illustrate the use of this approach for assessing neurotoxicity.
O'Callaghan
J P
JP
Neurotoxicology Division (MD-74B), United States Environmental Protection Agency, Research Triangle Park, NC 27711.
D000818:Animals; D001663:Bilirubin / Q000633:toxicity; D015415:Biomarkers / Q000032:analysis*; D001921:Brain / Q000187:drug effects / Q000473:pathology*; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis*; D009419:Nerve Tissue Proteins / Q000032:analysis*; D009457:Neuroglia / Q000187:drug effects / Q000473:pathology*; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D009498:Neurotoxins / Q000633:toxicity*; D051381:Rats; D014267:Triethyltin Compounds / Q000633:toxicity
D015415:Biomarkers; D005904:Glial Fibrillary Acidic Protein; D009419:Nerve Tissue Proteins; D009498:Neurotoxins; D014267:Triethyltin Compounds; C031575:triethyltin; D001663:Bilirubin