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Learning against the Background of DNA Methyltransferase Inhibition Leads to the Formation of Memory That Is Resistant to Reactivation and Impairment

  • GENERAL PATHOLOGY AND PATHOPHYSIOLOGY
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Bulletin of Experimental Biology and Medicine Aims and scope

The involvement of DNA methylation in the mechanisms of formation of conditioned food aversion memory was studied on Helix lucorum snails. The dynamics of aversion formation in snails injected with DNA methyltransferase inhibitor RG108 did not differ from that in control snails. The memory was retained for more than one month after training following RG108 injection and the duration of memory persistence did not differ from that in control animals. However, the characteristics of memory in control and experimental snails differed significantly. In control snails, injections of glutamate NMDA-receptor antagonist or protein synthesis inhibitor before memory retrieval caused disorders in the memory reconsolidation and development of amnesia 2 days after training. By contrast, injections of these substances before retrieval to snails trained against the background of RG108 treatment caused no memory disorders. We hypothesized that inhibition of DNA methylation processes led to the formation of strong memory, not reactivated after retrieval and not transformed into a labile state sensitive to amnesic agents.

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References

  1. Nikitin VP, Kozyrev SA, Solntseva SV. Peculiarities of Participation of DNA Methyltransferases in the Mechanisms of Storage, Impairment, and Recovery of Conditioned Food Aversion Memory. Bull. Exp. Biol. Med. 2018;166(1):1-6. doi: https://doi.org/10.1007/s10517-018-4275-7

    Article  CAS  PubMed  Google Scholar 

  2. Alberini CM. The role of reconsolidation and the dynamic process of long-term memory formation and storage. Front. Behav. Neurosci. 2011;5:12. doi: https://doi.org/10.3389/fnbeh.2011.00012

    Article  PubMed  PubMed Central  Google Scholar 

  3. Biergans SD, Jones JC, Treiber N, Galizia CG, Szyszka P. DNA methylation mediates the discriminatory power of associative long-term memory in honeybees. PLoS One. 2012;7(6):e39349. doi: https://doi.org/10.1371/journal.pone.0039349

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Feng J, Zhou Y, Campbell SL, Le T, Li E, Sweatt JD, Silva AJ, Fan G. Dnmt1 and Dnmt3a maintain DNA methylation and regulate synaptic function in adult forebrain neurons. Nat. Neurosci. 2010;13(4):423-430.

    Article  CAS  Google Scholar 

  5. Finnie PS, Nader K. The role of metaplasticity mechanisms in regulating memory destabilization and reconsolidation. Neurosci. Biobehav. Rev. 2012;36(7):1667-1707.

    Article  Google Scholar 

  6. Jarome TJ, Lubin FD. Epigenetic mechanisms of memory formation and reconsolidation. Neurobiol. Learn. Mem. 2014;115:116-127.

    Article  CAS  Google Scholar 

  7. Kim S, Kaang BK. Epigenetic regulation and chromatin remodeling in learning and memory. Exp. Mol. Med. 2017;49(1):e281. doi: https://doi.org/10.1038/emm.2016.140

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Lukowiak K, Heckler B, Bennett TE, Schriner EK, Wyrick K, Jewett C, Todd RP, Sorg BA. Enhanced memory persistence is blocked by a DNA methyltransferase inhibitor in the snail Lymnaea stagnalis. J. Exp. Biol. 2014;217(Pt 16):2920-2929.

  9. Miller CA, Sweatt JD. Covalent modification of DNA regulates memory formation. Neuron. 2007;53(6):857-869.

    Article  CAS  Google Scholar 

  10. Mitchnick KA, Creighton S, O’Hara M, Kalisch BE, Winters BD. Differential contributions of de novo and maintenance DNA methyltransferases to object memory processing in the rat hippocampus and perirhinal cortex--a double dissociation. Eur. J. Neurosci. 2015;41(6):773-786.

    Article  Google Scholar 

  11. Monsey MS, Ota KT, Akingbade IF, Hong ES, Schafe GE. Epigenetic alterations are critical for fear memory consolidation and synaptic plasticity in the lateral amygdala. PLoS One. 2011;6(5):e19958. doi: https://doi.org/10.1371/journal.pone.0019958

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Moroz LL, Kohn AB. Do different neurons age differently? Direct genome-wide analysis of aging in single identified cholinergic neurons. Front. Aging Neurosci. 2010;2. pii: 6. doi: 10.3389/neuro.24.006.2010

  13. Nikitin VP, Solntseva SV, Nikitin PV, Kozyrev SA. The role of DNA methylation in the mechanisms of memory reconsolidation and development of amnesia. Behav. Brain Res. 2015;279:148-154.

    Article  CAS  Google Scholar 

  14. Pearce K, Cai D, Roberts AC, Glanzman DL. Role of protein synthesis and DNA methylation in the consolidation and maintenance of long-term memory in Aplysia. Elife. 2017;6:e18299. doi: https://doi.org/10.7554/eLife.18299

    Article  PubMed  PubMed Central  Google Scholar 

  15. Rajasethupathy P, Antonov I, Sheridan R, Frey S, Sander C, Tuschl T, Kandel ER. A role for neuronal piRNAs in the epigenetic control of memory-related synaptic plasticity. Cell. 2012;149(3):693-707.

    Article  CAS  Google Scholar 

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Correspondence to P. V. Nikitin.

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Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 170, No. 9, pp. 274-280, September, 2020

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Solntseva, S.V., Nikitin, P.V., Kozyrev, S.A. et al. Learning against the Background of DNA Methyltransferase Inhibition Leads to the Formation of Memory That Is Resistant to Reactivation and Impairment. Bull Exp Biol Med 170, 288–293 (2021). https://doi.org/10.1007/s10517-021-05053-2

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  • DOI: https://doi.org/10.1007/s10517-021-05053-2

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