Glia increase degeneration of hippocampal neurons through release of tumor necrosis factor-alpha.
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 system in vivo, on a sandwich co-culture of neurons and glia. Exposure of a 98% pure culture of rat hippocampal neurons to 0.1-1 microM 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-alpha). Neuronal apoptosis and TNF-alpha 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-alpha antibody prevented the increase in neuronal apoptosis, and TNF-alpha administration induced apoptosis in hippocampal cells. We conclude that glial cells and TNF-alpha both modulate trimethyltin-induced neurodegeneration.
Viviani
B
B
Institute of Pharmacological Sciences, University of Milan, Italy.
Corsini
E
E
Galli
C L
CL
Marinovich
M
M
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001253:Astrocytes / Q000187:drug effects / Q000473:pathology; D002450:Cell Communication; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology*; D017628:Microglia / Q000187:drug effects / Q000473:pathology; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000473:pathology; D009457:Neuroglia / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014298:Trimethyltin Compounds / Q000633:toxicity; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism*
D004791:Enzyme Inhibitors; D011448:Prostaglandin Antagonists; D014298:Trimethyltin Compounds; D014409:Tumor Necrosis Factor-alpha; C046488:trimethyltin