Role of DNA Methylation in Mechanisms of Anterograde Amnesia

Abstract Previously, we found that impairment of conditioned food aversion memory consolidation or reconsolidation in snails by NMDA glutamate receptors antagonists led to the induction of amnesia changing over time. In particular, at the later amnesia stages (10 or more days), repeated aversion training for the same food type that was used in the initial training did not induce long-term memory formation. In these animals, long-term aversion memory for a new food type was formed. We characterized this amnesia as specific anterograde amnesia. In the present work, using DNA methyltransferases (DNMT) inhibitors, the DNA methylation processes role in mechanisms of anterograde amnesia and recovery from amnesia was investigated. It was found that in amnestic animals, DNMT inhibitor administration before or after repeated training led to the rapid long-term conditioned food aversion memory formation. It depended on proteins and mRNA synthesis at certain time windows. Thus, protein synthesis inhibitors administration before or immediately after repeated training, or RNA synthesis inhibitor injection after training, prevented memory formation induced by the DNMT inhibitor. The effects of DNMT inhibitors were specific for certain conditioned stimulus, since these inhibitors did not affect amnestic animals training for a new food stimulus. DNMT inhibition during second training removed blockade of these genes' expression, opening up access to them for transcription factors synthesized during training. Thus, this work was the first to study the molecular mechanisms of anterograde amnesia, as well as memory recovery, which can be important for search for pharmacological correction of this neuropsychic pathology.