Glia Increase Degeneration of Hippocampal Neurons through Release of Tumor Necrosis Factor-α

Abstract

This study characterizes the role of glial cells in chemically induced neurodegeneration. We evaluated the effect of trimethyltin, a trisubstituted organotin compound that elicits distinct lesions in the central nervous systemin vivo,on a sandwich co-culture of neurons and glia. Exposure of a 98% pure culture of rat hippocampal neurons to 0.1–1 μM trimethyltin for 24 h caused neural cell death and nuclear changes typical of apoptosis; at these doses glial cells viability was not affected but the cells released significant amounts of tumor necrosis factor-alpha (TNF-α). Neuronal apoptosis and TNF-α release from glial cells both increased when the two cell types were exposed together to trimethyltin, which indicates synergy. Treatment of a neuron–glia co-culture with TNF-α antibody prevented the increase in neuronal apoptosis, and TNF-α administration induced apoptosis in hippocampal cells. We conclude that glial cells and TNF-α both modulate trimethyltin-induced neurodegeneration.