scholarly journals Effect of Histone Deacetylase Inhibitor on Ethanol Withdrawal-Induced Hyperalgesia in Rats

2019 ◽  
Vol 22 (8) ◽  
pp. 523-527 ◽  
Author(s):  
Amynah A Pradhan ◽  
Alycia F Tipton ◽  
Huaibo Zhang ◽  
Areeb Akbari ◽  
Subhash C Pandey
Keyword(s):  
Histone Deacetylase ◽  
Alcohol Withdrawal ◽  
Histone Deacetylase Inhibitor ◽  
Pain Sensitivity ◽  
Histone Deacetylase Inhibitors ◽  
Ethanol Exposure ◽  
Ethanol Withdrawal ◽  
Chronic Ethanol ◽  
Chronic Ethanol Exposure ◽  
Deacetylase Inhibitor

Abstract Background Increased pain sensitivity is observed following alcohol withdrawal, and attempts to alleviate this hyperalgesia can contribute to the cycle of addiction. The aim of this study was to determine if alcohol withdrawal-induced hyperalgesia was observed in a chronic ethanol exposure model and if this pain was affected by histone deacetylase inhibitors, thus revealing an epigenetic mechanism. Methods Adult male Sprague Dawley rats received Lieber-DeCarli liquid control or ethanol (9% v/v) diet for 15 days. Mechanical sensitivity was measured with von Frey hair stimulation of the hindpaw during ethanol administration and 24- and 72-hour withdrawal. Results Ethanol withdrawal produced severe and sustained mechanical hyperalgesia, an effect not observed in the control or ethanol-maintained groups. Furthermore, this hyperalgesia was attenuated by the histone deacetylase inhibitor, suberoylanilide hydroxamic acid treatment. Conclusions Heightened pain sensitivity was observed following withdrawal from chronic ethanol exposure, and histone deacetylase inhibitors could be novel treatments for this alcohol withdrawal-induced hyperalgesia.

scholarly journals Interaction Between Social Defeat Stress and Chronic Ethanol Exposure on Behaviors During Ethanol Withdrawal and Pro-Inflammatory Cytokines in Mice

2021 ◽  
Vol 2 ◽  
pp. 1-11
Author(s):  
Gessynger Morais-Silva ◽  
Pedro B. Portilho ◽  
Juliana Fernandes-Santos ◽  
Rafaella M. Queiroz ◽  
Simone R. Deconte ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Social Defeat ◽  
Ethanol Exposure ◽  
Ethanol Withdrawal ◽  
Chronic Ethanol ◽  
Social Defeat Stress ◽  
Chronic Ethanol Exposure ◽  
Pro Inflammatory Cytokines

scholarly journals Withdrawal from Chronic Ethanol Exposure Increases Postsynaptic Glutamate Function of Insular Cortex Projections to the Rat Basolateral Amygdala

2019 ◽  
Author(s):  
Molly M. McGinnis ◽  
Brian C. Parrish ◽  
Brian A. McCool
Keyword(s):  
Synaptic Plasticity ◽  
Negative Affect ◽  
Basolateral Amygdala ◽  
Glutamate Release ◽  
Insular Cortex ◽  
Ethanol Exposure ◽  
Ethanol Withdrawal ◽  
Chronic Ethanol ◽  
Chronic Ethanol Exposure ◽  
Chronic Intermittent Ethanol

AbstractA key feature of alcohol use disorder (AUD) is negative affect during withdrawal, which often contributes to relapse and is thought to be caused by altered brain function, especially in circuits that are important mediators of emotional behaviors. Both the agranular insular cortex (AIC) and the basolateral amygdala (BLA) regulate emotions and are sensitive to ethanol-induced changes in synaptic plasticity. The AIC and BLA are reciprocally connected, however, and the effects of chronic ethanol exposure on this circuit have yet to be explored. Here, we use a combination of optogenetics and electrophysiology to examine the pre- and postsynaptic changes that occur to AIC – BLA synapses following withdrawal from 7- or 10-days of chronic intermittent ethanol (CIE) exposure. While CIE/withdrawal did not alter presynaptic glutamate release probably from AIC inputs, withdrawal from 10, but not 7, days of CIE increased AMPA receptor-mediated postsynaptic function at these synapses. Additionally, NMDA receptor-mediated currents evoked by electrical stimulation of the external capsule, which contains AIC afferents, were also increased during withdrawal. Notably, a single subanesthetic dose of ketamine administered at the onset of withdrawal prevented the withdrawal-induced increases in both AMPAR and NMDAR postsynaptic function. Ketamine also prevented the withdrawal-induced increases in anxiety-like behavior measured using the elevated zero maze. Together, these findings suggest that chronic ethanol exposure increases postsynaptic function within the AIC – BLA circuit and that ketamine can prevent ethanol withdrawal-induced alterations in synaptic plasticity and negative affect.

scholarly journals MAPK pathway activation leads to Bim loss and histone deacetylase inhibitor resistance: rationale to combine romidepsin with an MEK inhibitor

Blood ◽  
2013 ◽  
Vol 121 (20) ◽  
pp. 4115-4125 ◽  
Author(s):  
Arup R. Chakraborty ◽  
Robert W. Robey ◽  
Victoria L. Luchenko ◽  
Zhirong Zhan ◽  
Richard L. Piekarz ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitor ◽  
Histone Deacetylase Inhibitors ◽  
Mapk Pathway ◽  
Mek Inhibitor ◽  
Pathway Activation ◽  
Deacetylase Inhibitor ◽  
Key Points ◽  
Inhibitor Resistance ◽  
Fundamental Mechanism

Key Points MAPK pathway activation and Bim loss may represent a fundamental mechanism of resistance to histone deacetylase inhibitors. Combination of romidepsin with an MEK inhibitor may lead to greater responses in cancers in which the MAPK pathway is active.

scholarly journals Tau Stabilizes Chromatin Compaction

2021 ◽  
Vol 9 ◽  
Author(s):  
Thomas Rico ◽  
Melissa Gilles ◽  
Alban Chauderlier ◽  
Thomas Comptdaer ◽  
Romain Magnez ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Histone Deacetylase ◽  
Chromatin Structure ◽  
Histone Deacetylase Inhibitor ◽  
Histone Deacetylase Inhibitors ◽  
Breast Cancer Cell Lines ◽  
Post Translational Modifications ◽  
Deacetylase Inhibitor ◽  
Extensive Body ◽  
Or Organization

An extensive body of literature suggested a possible role of the microtubule-associated protein Tau in chromatin functions and/or organization in neuronal, non-neuronal, and cancer cells. How Tau functions in these processes remains elusive. Here we report that Tau expression in breast cancer cell lines causes resistance to the anti-cancer effects of histone deacetylase inhibitors, by preventing histone deacetylase inhibitor-inducible gene expression and remodeling of chromatin structure. We identify Tau as a protein recognizing and binding to core histone when H3 and H4 are devoid of any post-translational modifications or acetylated H4 that increases the Tau’s affinity. Consistent with chromatin structure alterations in neurons found in frontotemporal lobar degeneration, Tau mutations did not prevent histone deacetylase-inhibitor-induced higher chromatin structure remodeling by suppressing Tau binding to histones. In addition, we demonstrate that the interaction between Tau and histones prevents further histone H3 post-translational modifications induced by histone deacetylase-inhibitor treatment by maintaining a more compact chromatin structure. Altogether, these results highlight a new cellular role for Tau as a chromatin reader, which opens new therapeutic avenues to exploit Tau biology in neuronal and cancer cells.

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