INHIBITORY EFFECTS OF ACTINOMYCIN-D AND CYCLOHEXIMIDE ON NEURONAL DEATH IN ADULT MANDUCA-SEXTA

A decline in circulating 20-hydroxyecdysone permits the emergence of t he adult Manduca sexta moth; this endocrine signal also triggers the d eath of approximately half of the neurons in the unfused abdomina,l ga nglia of the moth central nervous system. This programmed death of neu rons was markedly reduced by treatment with either actinomycin D (an R NA synthesis inhibitor) or cycloheximide (a protein synthesis inhibito r). Similar results were found after addition of these agents to ventr al nerve cord cultures. The effectiveness of these treatments in delay ing or blocking neuronal death depended upon their time of administrat ion relative to the normal time of postemergence death in the particul ar motoneuron under study: late-dying neurons, for example, could stil l be saved by these treatments even after early-dying neurons had alre ady initiated degeneration. In both intact moths and cultured ventral nerve cords, the ability of actinomycin D to prevent neuronal death wa ned at the same time at which replacement of the steroid hormone could no longer block neuronal death. This suggests that the steroid commit ment point represents the time at which the genes that mediate cell de ath are transcribed. Cycloheximide remained effective in delaying or b locking neuronal death until shortly before the onset of degeneration, suggesting that ongoing protein synthesis is essential for the initia tion of the degeneration response. (C) 1994 John Wiley and Sons, Inc.