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Modulation of PARP-1 Activity in a Broad Time Window Attenuates Memorizing Fear

The amygdala plays a critical role in the acquisition and consolidation of fear-related memories. Recent studies have demonstrated that ADP-ribosylation of histones, accelerated by PARPs, affects the chromatin structure and the binding of chromatin remodeling complexes with transcription factors. In...

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Autores principales: Elharrar, Einat, Dikshtein, Yahav, Meninger-Mordechay, Sapir, Lichtenstein, Yehuda, Yadid, Gal
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8226584/
https://www.ncbi.nlm.nih.gov/pubmed/34201014
http://dx.doi.org/10.3390/ijms22126170
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author Elharrar, Einat
Dikshtein, Yahav
Meninger-Mordechay, Sapir
Lichtenstein, Yehuda
Yadid, Gal
author_facet Elharrar, Einat
Dikshtein, Yahav
Meninger-Mordechay, Sapir
Lichtenstein, Yehuda
Yadid, Gal
author_sort Elharrar, Einat
collection PubMed
description The amygdala plays a critical role in the acquisition and consolidation of fear-related memories. Recent studies have demonstrated that ADP-ribosylation of histones, accelerated by PARPs, affects the chromatin structure and the binding of chromatin remodeling complexes with transcription factors. Inhibition of PARP-1 activity during the labile phase of re-consolidation may erase memory. Accordingly, we investigated the possibility of interfering with fear conditioning by PARP-1 inhibition. Herein, we demonstrate that injection of PARP-1 inhibitors, specifically into the CeA or i.p., in different time windows post-retrieval, attenuates freezing behavior. Moreover, the association of memory with pharmacokinetic timing of PARP inhibitor arrival to the brain enabled/achieved attenuation of a specific cue-associated memory of fear but did not hinder other memories (even traumatic events) associated with other cues. Our results suggest using PARP-1 inhibitors as a new avenue for future treatment of PTSD by disrupting specific traumatic memories in a broad time window, even long after the traumatic event. The safety of using these PARP inhibitors, that is, not interfering with other natural memories, is an added value.
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spelling pubmed-82265842021-06-26 Modulation of PARP-1 Activity in a Broad Time Window Attenuates Memorizing Fear Elharrar, Einat Dikshtein, Yahav Meninger-Mordechay, Sapir Lichtenstein, Yehuda Yadid, Gal Int J Mol Sci Article The amygdala plays a critical role in the acquisition and consolidation of fear-related memories. Recent studies have demonstrated that ADP-ribosylation of histones, accelerated by PARPs, affects the chromatin structure and the binding of chromatin remodeling complexes with transcription factors. Inhibition of PARP-1 activity during the labile phase of re-consolidation may erase memory. Accordingly, we investigated the possibility of interfering with fear conditioning by PARP-1 inhibition. Herein, we demonstrate that injection of PARP-1 inhibitors, specifically into the CeA or i.p., in different time windows post-retrieval, attenuates freezing behavior. Moreover, the association of memory with pharmacokinetic timing of PARP inhibitor arrival to the brain enabled/achieved attenuation of a specific cue-associated memory of fear but did not hinder other memories (even traumatic events) associated with other cues. Our results suggest using PARP-1 inhibitors as a new avenue for future treatment of PTSD by disrupting specific traumatic memories in a broad time window, even long after the traumatic event. The safety of using these PARP inhibitors, that is, not interfering with other natural memories, is an added value. MDPI 2021-06-08 /pmc/articles/PMC8226584/ /pubmed/34201014 http://dx.doi.org/10.3390/ijms22126170 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Elharrar, Einat
Dikshtein, Yahav
Meninger-Mordechay, Sapir
Lichtenstein, Yehuda
Yadid, Gal
Modulation of PARP-1 Activity in a Broad Time Window Attenuates Memorizing Fear
title Modulation of PARP-1 Activity in a Broad Time Window Attenuates Memorizing Fear
title_full Modulation of PARP-1 Activity in a Broad Time Window Attenuates Memorizing Fear
title_fullStr Modulation of PARP-1 Activity in a Broad Time Window Attenuates Memorizing Fear
title_full_unstemmed Modulation of PARP-1 Activity in a Broad Time Window Attenuates Memorizing Fear
title_short Modulation of PARP-1 Activity in a Broad Time Window Attenuates Memorizing Fear
title_sort modulation of parp-1 activity in a broad time window attenuates memorizing fear
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8226584/
https://www.ncbi.nlm.nih.gov/pubmed/34201014
http://dx.doi.org/10.3390/ijms22126170
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