NEUROTOXICITY OF TUNICAMYCIN ON CULTURED CEREBELLAR GRANULE CELLS

Tunicamycin (TM) is known to cause severe neurological diseases in the central nervous system of animals. Cultured cerebellar granule cells were used to investigate the direct cytotoxicity of this agent on cere bellar neurons. Results indicate that TM is a potent inhibitor of glyc osylation and protein synthesis. This agent killed cerebellar granule cells in a dose and time-dependent manner. TM treatment of these neuro ns led to atrophic cell bodies and condensed nuclei. This TM-induced c ell death could be prevented by cycloheximide and aurintricarboxylic a cid. In contrast, TM had no apparent toxicity toward nerve growth fact or-differentiated PC12 cells under similar conditions. These results s uggest that TM kills cerebellar granule cells in a manner similar to p rogrammed cell death. (C) 1997 Inter Press, Inc.