Trimethyltin-evoked neuronal apoptosis and glia response in mixed cultures of rat hippocampal dentate gyrus: a new model for the study of the cell type-specific influence of neurotoxins

We investigated the effects of a potent neurotoxin, trimethyltin (TMT), on mixed neuronal/glial cultures derived from rat hippocampal dentate gyrus. We found that TMT induced neuronal cell death in a concentration dependent manner, which was estimated by microtubule degeneration, hematoxylin histological staining and the TUNEL method. This cell death is most probably of an apoptotic type as suggested by Hoechst staining. In parallel to studies the effects of TMT on neurons, its concentration dependent actions on astroglia and microglia were also examined using GFAP and GS-B4 isolectin as immunocytochemical markers, respectively. We found that neurotoxic concentrations of TMT evoked astrocytic swelling, whereas low, non-cytotoxic concentrations caused changes in microglia morphology characteristic of their active form. The combined results of our studies provide new data concerning the cell type-specific influence of TMT and indicate that the culture of dentate gyrus cells is a feasible in vitro modelforfurther studies of neuronal-glial interaction in response to toxic injury.