{"title":"聚 ADP- 核糖基化调节 Arc 的表达，促进适应性应激反应。","authors":"Eliyahu Dahan, Leah Pergamenshik, Tze'ela Taub, Arthur Vovk, Jade Manier, Raphael Avneri, Elad Lax","doi":"10.1007/s00213-025-06744-8","DOIUrl":null,"url":null,"abstract":"<p><strong>Rationale: </strong>Rapid adaptation to stressful events is essential for survival and requires acute stress response and stress-coping strategy. However, the molecular mechanisms that govern this coping strategy have yet to be fully discovered.</p><p><strong>Objectives: </strong>This study aims to investigate the effects of poly ADP-ribosylation (PARylation) on stress-coping strategies following acute stress and to identify the target genes influenced by Parp1-induced histone PARylation.</p><p><strong>Methods: </strong>Mice were subjected to a forced swim test, a well-established acute stress paradigm, to evaluate cortical PARylation and assess the expression of activity-dependent genes. The pharmacological inhibition of Parp1 was conducted using ABT888 (Veliparib) to determine its effects on stress-coping behavior and related molecular changes.</p><p><strong>Results: </strong>The forced swim test increased cortical PARylation and upregulated the expression of activity-dependent genes. Systemic inhibition of Parp1 with ABT888 led to impaired stress-coping behavior, evidenced by a reduced immobility response during a subsequent forced swim test done 24 hours later. This impairment was associated with decreased chromatin PARylation and histone H4 acetylation at the Arc promoter and reduced Arc expression observed one hour after Parp1 inhibition.</p><p><strong>Conclusion: </strong>Our findings indicate that chromatin PARylation at the Arc promoters regulates histone H4 acetylation and Arc gene expression, and a subsequent impact on successful stress-coping behavior in response to acute stress.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5000,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Poly ADP-ribosylation regulates Arc expression and promotes adaptive stress-coping.\",\"authors\":\"Eliyahu Dahan, Leah Pergamenshik, Tze'ela Taub, Arthur Vovk, Jade Manier, Raphael Avneri, Elad Lax\",\"doi\":\"10.1007/s00213-025-06744-8\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Rationale: </strong>Rapid adaptation to stressful events is essential for survival and requires acute stress response and stress-coping strategy. However, the molecular mechanisms that govern this coping strategy have yet to be fully discovered.</p><p><strong>Objectives: </strong>This study aims to investigate the effects of poly ADP-ribosylation (PARylation) on stress-coping strategies following acute stress and to identify the target genes influenced by Parp1-induced histone PARylation.</p><p><strong>Methods: </strong>Mice were subjected to a forced swim test, a well-established acute stress paradigm, to evaluate cortical PARylation and assess the expression of activity-dependent genes. The pharmacological inhibition of Parp1 was conducted using ABT888 (Veliparib) to determine its effects on stress-coping behavior and related molecular changes.</p><p><strong>Results: </strong>The forced swim test increased cortical PARylation and upregulated the expression of activity-dependent genes. Systemic inhibition of Parp1 with ABT888 led to impaired stress-coping behavior, evidenced by a reduced immobility response during a subsequent forced swim test done 24 hours later. This impairment was associated with decreased chromatin PARylation and histone H4 acetylation at the Arc promoter and reduced Arc expression observed one hour after Parp1 inhibition.</p><p><strong>Conclusion: </strong>Our findings indicate that chromatin PARylation at the Arc promoters regulates histone H4 acetylation and Arc gene expression, and a subsequent impact on successful stress-coping behavior in response to acute stress.</p>\",\"PeriodicalId\":20783,\"journal\":{\"name\":\"Psychopharmacology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.5000,\"publicationDate\":\"2025-01-14\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Psychopharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s00213-025-06744-8\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Psychopharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00213-025-06744-8","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
Poly ADP-ribosylation regulates Arc expression and promotes adaptive stress-coping.
Rationale: Rapid adaptation to stressful events is essential for survival and requires acute stress response and stress-coping strategy. However, the molecular mechanisms that govern this coping strategy have yet to be fully discovered.
Objectives: This study aims to investigate the effects of poly ADP-ribosylation (PARylation) on stress-coping strategies following acute stress and to identify the target genes influenced by Parp1-induced histone PARylation.
Methods: Mice were subjected to a forced swim test, a well-established acute stress paradigm, to evaluate cortical PARylation and assess the expression of activity-dependent genes. The pharmacological inhibition of Parp1 was conducted using ABT888 (Veliparib) to determine its effects on stress-coping behavior and related molecular changes.
Results: The forced swim test increased cortical PARylation and upregulated the expression of activity-dependent genes. Systemic inhibition of Parp1 with ABT888 led to impaired stress-coping behavior, evidenced by a reduced immobility response during a subsequent forced swim test done 24 hours later. This impairment was associated with decreased chromatin PARylation and histone H4 acetylation at the Arc promoter and reduced Arc expression observed one hour after Parp1 inhibition.
Conclusion: Our findings indicate that chromatin PARylation at the Arc promoters regulates histone H4 acetylation and Arc gene expression, and a subsequent impact on successful stress-coping behavior in response to acute stress.
期刊介绍：
Official Journal of the European Behavioural Pharmacology Society (EBPS)
Psychopharmacology is an international journal that covers the broad topic of elucidating mechanisms by which drugs affect behavior. The scope of the journal encompasses the following fields:
Human Psychopharmacology: Experimental
This section includes manuscripts describing the effects of drugs on mood, behavior, cognition and physiology in humans. The journal encourages submissions that involve brain imaging, genetics, neuroendocrinology, and developmental topics. Usually manuscripts in this section describe studies conducted under controlled conditions, but occasionally descriptive or observational studies are also considered.
Human Psychopharmacology: Clinical and Translational
This section comprises studies addressing the broad intersection of drugs and psychiatric illness. This includes not only clinical trials and studies of drug usage and metabolism, drug surveillance, and pharmacoepidemiology, but also work utilizing the entire range of clinically relevant methodologies, including neuroimaging, pharmacogenetics, cognitive science, biomarkers, and others. Work directed toward the translation of preclinical to clinical knowledge is especially encouraged. The key feature of submissions to this section is that they involve a focus on clinical aspects.
Preclinical psychopharmacology: Behavioral and Neural
This section considers reports on the effects of compounds with defined chemical structures on any aspect of behavior, in particular when correlated with neurochemical effects, in species other than humans. Manuscripts containing neuroscientific techniques in combination with behavior are welcome. We encourage reports of studies that provide insight into the mechanisms of drug action, at the behavioral and molecular levels.
Preclinical Psychopharmacology: Translational
This section considers manuscripts that enhance the confidence in a central mechanism that could be of therapeutic value for psychiatric or neurological patients, using disease-relevant preclinical models and tests, or that report on preclinical manipulations and challenges that have the potential to be translated to the clinic. Studies aiming at the refinement of preclinical models based upon clinical findings (back-translation) will also be considered. The journal particularly encourages submissions that integrate measures of target tissue exposure, activity on the molecular target and/or modulation of the targeted biochemical pathways.
Preclinical Psychopharmacology: Molecular, Genetic and Epigenetic
This section focuses on the molecular and cellular actions of neuropharmacological agents / drugs, and the identification / validation of drug targets affecting the CNS in health and disease. We particularly encourage studies that provide insight into the mechanisms of drug action at the molecular level. Manuscripts containing evidence for genetic or epigenetic effects on neurochemistry or behavior are welcome.
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