The Use of Microglia Activation in the Evaluation of Neurotoxicity

Abstract

The toxicities of the therapeutic drugs amitriptyline and diazepam, the metal compounds methyl mercury and triethyllead, and the essential fatty acids linoleic acid and α-linolenic acid, were determined in a system of rat glial cells in culture with microglia activation as the parameter for evaluation of toxicity. The markers of activated microglia — increased expression of complement receptor 3 and transformation of microglia to phagocytes — were evaluated by immunocytochemical staining with the monoclonal antibody OX-42 and after incubation with fluorescent latex beads. Concentrations which activated microglial cells were compared to EC50 values from acute toxicity tests, and to concentrations which in previous studies activated oligodendroglial cells. The results show that the drugs amitriptyline and diazepam, and fatty acids linoleic acid and α-linolenic acid, activated microglia at 10–25 times lower levels when compared to the EC50 values. Microglia activation was induced by α-linolenic acid and amitriptyline at about 10 times lower levels when compared to linoleic acid and diazepam. The microglia activating concentrations of the metal compounds were, 1,000 times lower, when compared to acute toxicity values. The activation of microglia was initiated by the same concentrations of the compounds that in previous studies were found to activate oligodendroglial cells.