rg108 and Amnesia

We studied the participation of DNA-methylation processes in the mechanisms of memory storage and reconsolidation, amnesia induction, and in recovery of the conditioned food aversion memory in edible snails. It was found that daily injections of DNA methyltransferases inhibitor over 3 days combined with a reminder of a conditioned food stimulus did not affect memory storage. The administration of DNA methyltransferase inhibitors did not suppress induction of amnesia caused the NMDA receptor antagonist/reminder. Injections of DNA methyltransferase inhibitors combined with the reminder led to memory recovery in 3 days after amnesia induction. Thus, DNA methyltransferase inhibitors in the same doses did not affect storage and reconsolidation of memory, as well as the mechanisms of amnesia induction. At the same time, injections of inhibitors led to memory recovery, apparently, due to disruption of reactivation and amnesia development.

Topics: Amnesia; Animals; DNA Modification Methylases; Helix, Snails; Memory; Phthalimides; Receptors, N-Methyl-D-Aspartate; Tryptophan; Valine

Current considerations suggest that the mechanisms of long term memory are based on the changes of the neuronal genetic algorithms. Process of the enzyme DNA methylation have great importance to the differential genes expression, and is likely to be one of the key mechanisms of the consolidation and memory storage. The present study aimed to investigate the DNA methylation processes role in the mechanisms of the conditioned food aversion memory reconsolidation and also in the amnesia development mechanisms, caused by disturbances of the reconsolidation in Helix lucorum. It was found that DNA-methyltransferase inhibitors zebularine and RG108 had no influence on the memory reconsolidation. We investigated the effects of the DNA-methyltransferase inhibitors on different amnesia stage. The amnesia was induced by NMDA glutamate receptors antagonists. At the early stage of amnesia (3rd day after its induction) injections of the DNA-methyltransferase inhibitors in combination with reminder by conditioned food stimuli led to memory recall. Memory was recovered by the DNA-methyltransferase inhibitors injections before the reminder and also 3h, but not 9h after the reminder. In case when enzyme inhibitors or reminders were applied separately, no effect on memory was revealed. At the late stage of amnesia (10th day) the DNA-methyltransferase inhibitors didn't affects amnesia development. It might be hypothesized that presentation of reminding stimuli result in the reactivation/reconsolidation of molecular processes, involved in amnesia development, one of the key mechanisms of which could be the DNA methylation/demethylation of neural cells.

Topics: Amnesia; Animals; Avoidance Learning; Cytidine; DNA Methylation; DNA Modification Methylases; Enzyme Inhibitors; Helix, Snails; Memory, Long-Term; Phthalimides; Tryptophan

We studied the role of DNA methylation in the mechanisms of amnesia in edible snails, which was induced by impairment of conditioned food aversion memory reconsolidation with NMDA glutamate receptor antagonist. The effects of DNA methyltransferase inhibitors were shown to depend on the stage of amnesia. At the early stage of amnesia (day 3 after induction), injections of methyltransferase inhibitors in combination with conditioned food stimulus (reminder) were followed by memory recovery. Application of inhibitors in the absence of the reminder was ineffective. Methyltransferase inhibitors were ineffective at the late stage of amnesia (day 10). Our results suggest that the presentation of reminding conditioned stimuli is followed by reactivation of amnesia. Methylation or demethylation of DNA in nerve cells serves as one of the key mechanisms for amnesia.

Topics: Amnesia; Animals; Conditioning, Psychological; Cytidine; Dizocilpine Maleate; DNA Methylation; DNA-Cytosine Methylases; Helix, Snails; Learning; Phthalimides; Receptors, N-Methyl-D-Aspartate; Tryptophan