Recovery of acetylcholinesterase activity after acute organophosphate treatment of CNS reaggregate cultures

Abstract

The effect of a single dose of diisopropylfluorophosphate on acetylcholinesterase (AChE) activity was examined in mouse CNS reaggregate cultures. At 17–24 days in culture, reaggregates were treated with 0.6 mg/liter DFP for 15 min. The recovery of AChE activity was examined in culture. After treatment, 5.4 ± 1.19% of control AChE activity remained. By 24 hr, 31.6 ± 6.4% of control activity had returned and the recovery of activity was essentially complete by 7 days after treatment. Recovery of AChE activity after DFP treatment required protein synthesis, since there was no recovery in the presence of cycloheximide. After treatment with the reversible inhibitor, physostigmine at 0.5 mg/ml, recovery of AChE activity was complete within 24 hr after treatment. These results indicate that CNS reaggregate cultures not only express differentiated functions of the CNS, but also have the capacity to turn over proteins, and thus may provide a good model system in which to examine mechanisms of toxicity.