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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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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. |
format | Online Article Text |
id | pubmed-8226584 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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