Role of DNA Methylation in Mechanisms of Anterograde Amnesia

Previously, we found that conditional food aversion memory reconsolidation impairment in snails by NMDA glutamate receptor antagonists led to the amnesia induction, in the late stages of which (>10 days) repeated training did not cause long-term memory formation. In the same animals, long-term memory aversion to a new food type was formed. We characterized this amnesia as specific anterograde amnesia. In the present work we studied the role of DNA methylation processes as well as protein and mRNA synthesis in the mechanisms of anterograde amnesia and memory recovery. It was found that in amnesic animals the DNMT-methyltransferase (DNMT) inhibitors administration before or after shortened repeated training led to the rapid long-term conditional food aversion formation (Ebbinhaus saving effect). This result suggests that amnestic animals retain a latent memory, which is the basis for accelerated memory formation during repeated training. Protein synthesis inhibitors administration before or immediately after repeated training or administration of RNA synthesis inhibitor after repeated training prevented memory formation under DNMT inhibitor action. The earlier protein synthesis inhibitor effect suggests that the proteins required for memory formation are translated from the pre-existing, translationally repressed mRNAs. Thus, the anterograde amnesia key mechanism is DNMT-dependent suppression of the transcription of genes involved in memory mechanisms. Inhibition of DNMT during repeated training reversed these genes expression blockade, opening access to them by transcription factors synthesized during training from the pre-existing mRNAs.