DNA methylation inhibition participates in the anterograde amnesia key mechanism through the suppression of the transcription of genes involved in memory formation in grape snails.

Autor: Solntseva SV; Laboratory of Functional Neurochemistry, P.K. Anokhin Institute of Normal Physiology, Moscow 125315, Russia. Electronic address: sols3@yandex.ru., Nikitin VP; Laboratory of Functional Neurochemistry, P.K. Anokhin Institute of Normal Physiology, Moscow 125315, Russia. Electronic address: nikitinpaulv@yandex.com., Kozyrev SA; Laboratory of Functional Neurochemistry, P.K. Anokhin Institute of Normal Physiology, Moscow 125315, Russia. Electronic address: sergej3591@mail.ru., Nikitin PV; Laboratory of Functional Neurochemistry, P.K. Anokhin Institute of Normal Physiology, Moscow 125315, Russia. Electronic address: redseadog@gmail.com.
Jazyk: angličtina
Zdroj: Behavioural brain research [Behav Brain Res] 2023 Feb 02; Vol. 437, pp. 114118. Date of Electronic Publication: 2022 Sep 16.
DOI: 10.1016/j.bbr.2022.114118
Abstrakt: The study of the amnesia mechanisms is of both theoretical and practical importance. The mechanisms of anterograde amnesia are the least studied, due to the lack of an experimental model that allows studying this amnesia type molecular and cellular mechanisms. 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 epigenetic DNA methylation processes as well as protein and mRNA synthesis in the mechanisms of anterograde amnesia and memory recovery. DNMT methyltransferase inhibitors (iDNMT: zebularine, RG108 (N-Phthalyl-1-tryptophan), and 5-AZA (5-Aza-2'-deoxycytidine)) were used to alter DNA methylation. It was found that in amnesic animals the iDNMT administration before or after shortened repeated training led to the rapid long-term conditional food aversion formation (Ebbinghaus 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 (cycloheximide) before or immediately after repeated training or administration of RNA synthesis inhibitor (actinomycin D) after repeated training prevented memory formation under iDNMT 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, we have shown for the first time that 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.
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Databáze: MEDLINE
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