title: The role of DNA methylation in the mechanisms of memory reconsolidation and development of amnesia.
abstract: 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.
authors.affiliation: Laboratory of Neurochemistry, P. K. Anokhin Institute of Normal Physiology, Russian Academy of Medical Sciences, Mokhovaya str. 11/4, 125009 Moscow, Russian Federation. Electronic address: nikitin.vp@mail.ru.
authors.forename: V P
authors.initials: VP
authors.lastname: Nikitin
authors.affiliation: Laboratory of Neurochemistry, P. K. Anokhin Institute of Normal Physiology, Russian Academy of Medical Sciences, Mokhovaya str. 11/4, 125009 Moscow, Russian Federation.
authors.forename: S V
authors.initials: SV
authors.lastname: Solntseva
authors.affiliation: Laboratory of Neurochemistry, P. K. Anokhin Institute of Normal Physiology, Russian Academy of Medical Sciences, Mokhovaya str. 11/4, 125009 Moscow, Russian Federation.
authors.forename: P V
authors.initials: PV
authors.lastname: Nikitin
authors.affiliation: Laboratory of Neurochemistry, P. K. Anokhin Institute of Normal Physiology, Russian Academy of Medical Sciences, Mokhovaya str. 11/4, 125009 Moscow, Russian Federation.
authors.forename: S A
authors.initials: SA
authors.lastname: Kozyrev
mesh_terms: D000647:Amnesia / Q000235:genetics*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D003562:Cytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006372:Helix, Snails; D057567:Memory, Long-Term / Q000187:drug effects / Q000502:physiology*; D010797:Phthalimides / Q000494:pharmacology; D014364:Tryptophan / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D010797:Phthalimides; C503639:RG108; D003562:Cytidine; C009131:pyrimidin-2-one beta-ribofuranoside; D014364:Tryptophan; D015254:DNA Modification Methylases
keywords: Amnesia; DNA methylation; Learning; Long-term memory; Reconsolidation; Snail