Modulation of PARP-1 Activity in a Broad Time Window Attenuates Memorizing Fear
Autor: | Sapir Meninger-Mordechay, Gal Yadid, Einat Elharrar, Yahav Dikshtein, Yehuda Lichtenstein |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Male QH301-705.5 PARP-1 Poly(ADP-ribose) Polymerase Inhibitors Traumatic memories Amygdala Article Catalysis Chromatin remodeling Inorganic Chemistry Rats Sprague-Dawley Stress Disorders Post-Traumatic 03 medical and health sciences 0302 clinical medicine Memory medicine Animals Fear conditioning Physical and Theoretical Chemistry Biology (General) Molecular Biology QD1-999 Spectroscopy Behavior Animal Chemistry Organic Chemistry Brain PTSD General Medicine Fear anxiety fear conditioning Computer Science Applications Chromatin Rats Freezing behavior 030104 developmental biology medicine.anatomical_structure memory consolidation PARP inhibitor central amygdala Memory consolidation Neuroscience 030217 neurology & neurosurgery |
Zdroj: | International Journal of Molecular Sciences, Vol 22, Iss 6170, p 6170 (2021) International Journal of Molecular Sciences Volume 22 Issue 12 |
ISSN: | 1661-6596 1422-0067 |
Popis: | 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. |
Databáze: | OpenAIRE |
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