Comparative Study of the Effect of a DNA Methyltransferase Inhibitor and a Histone Deacetylase Inhibitor on Memory Formation Processes in Anterograde Amnesia.

Abstract

The participation of DNA methylation and histone acetylation in the mechanisms of anterograde amnesia and memory recovery was studied on grape snails trained in conditioned food aversion. Anterograde amnesia developed 10 days after memory reconsolidation impairment with an NMDA glutamate receptor antagonist and was characterized by long-term memory formation impairment upon repeated training. DNA methyltransferase inhibitor injections to snails 1 h before repeated training, as well as 15 min or 4 h after repeated training, caused rapid formation of memory that persisted for at least 10 days. Injections of histone deacetylase inhibitor before repeated training also induced the formation of a stable long-term memory. However, administration of histone deacetylase inhibitor 15 min after repeated training initiated a temporary memory recovery. Injections of the inhibitor 4 h after repeated training were ineffective. These results indicate that histone-dependent chromatin remodeling and DNA methylation are selectively involved in the mechanisms of anterograde amnesia and memory recovery.