Changes in histone acetylation in the prefrontal cortex of ethanol-exposed adolescent rats are associated with ethanol-induced place conditioning

Pascual, Marı́a; Couto, Bruno Ribeiro Do; Alfonso-Loeches, Silvia; Aguilar, M.A.; Rodrı́guez-Arias, Marta

doi:10.1016/j.neuropharm.2012.01.011

Cited by 116 publications

(95 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Several classes of HDAC inhibitors, including NaBu, TSA, vorinostat, and hydroxamic acid, have been shown to inhibit HDAC activity and shift the overall balance in favor of enhanced HAT activity (Yang and Seto, 2007;Pascual et al, 2012). Consistent with those previous findings, the present data show that treatment with ATRA and NaBu significantly reduced HDAC activity and increased HAT activity in Npr1 1-copy mice.…”

Section: Discussionsupporting

confidence: 91%

All-Trans Retinoic Acid and Sodium Butyrate Enhance Natriuretic Peptide Receptor A Gene Transcription: Role of Histone Modification

et al. 2014

View full text Add to dashboard Cite

The objective of the present study was to delineate the mechanisms of GC-A/natriuretic peptide receptor-A (GC-A/ NPRA) gene (Npr1) expression in vivo. We used all-trans retinoic acid (ATRA) and histone deacetylase (HDAC) inhibitor, sodium butyrate (NaBu) to examine the expression and function of Npr1 using gene-disrupted heterozygous (1-copy; 1/2), wild-type (2-copy; 1/1), and gene-duplicated heterozygous (3-copy; 11/1) mice. Npr1 1/2 mice exhibited increased renal HDAC and reduced histone acetyltransferase (HAT) activity; on the contrary, Npr111/1 mice showed decreased HDAC and enhanced HAT activity compared with Npr1 1/1 mice. ATRA and NaBu promoted global acetylation of histones H3-K9/14 and H4-K12, reduced methylation of H3-K9 and H3-K27, and enriched accumulation of active chromatin marks at the Npr1 promoter. A combination of ATRA-NaBu promoted recruitment of activator-complex containing E26 transformation-specific 1, retinoic acid receptor a, and HATs (p300 and p300/cAMP response element-binding protein-binding protein-associated factor) at the Npr1 promoter, and significantly increased renal NPRA expression, GC activity, and cGMP levels. Untreated 1-copy mice showed significantly increased systolic blood pressure and renal expression of a-smooth muscle actin (a-SMA) and proliferating cell nuclear antigen (PCNA) compared with 2-and 3-copy mice. Treatment with ATRA and NaBu synergistically attenuated the expression of a-SMA and PCNA and reduced systolic blood pressure in Npr1 1/2 mice. Our findings demonstrate that epigenetic upregulation of Npr1 gene transcription by ATRA and NaBu leads to attenuation of renal fibrotic markers and systolic blood pressure in mice with reduced Npr1 gene copy number, which will have important implications in prevention and treatment of hypertension-related renal pathophysiological conditions.

show abstract

Section: Discussionsupporting

confidence: 91%

All-Trans Retinoic Acid and Sodium Butyrate Enhance Natriuretic Peptide Receptor A Gene Transcription: Role of Histone Modification

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Numerous studies have used histone deacetylase inhibitor TSA to determine the involvement of histone acetylation in brain disorders associated with ethanol (Pascual et al, 2012;You et al, 2014). Using TSA, we determined whether histone acetylation is an upstream mediator that triggers EW-induced mitochondrial respiratory damage.…”

Section: Resultsmentioning

confidence: 99%

“…Acetate is converted to acetylcoenzyme A (Ugarte and Iturriaga, 1976), which is required by histone acetyltransferase to acetylate histone (Breen et al, 1971;Smith et al, 1987). On the other hand, an increase or a decrease in histone acetylation has been reported in the brain of EW rats (Pandey et al, 2008;Pascual et al, 2012). These studies show that aberrant histone acetylation may mediate ethanol consumption or EW-related central nervous system disorders, making them important drug targets to manage alcoholism.…”

Section: Introductionmentioning

confidence: 96%

Aberrant Histone Acetylation Promotes Mitochondrial Respiratory Suppression in the Brain of Alcoholic Rats

Jung

Metzger

2014

J Pharmacol Exp Ther

View full text Add to dashboard Cite

The acetylation of histone proteins in the core of DNA regulates gene expression, including those affecting mitochondria. Both histone acetylation and mitochondrial deficit have been implicated in neuronal damage associated with drinking problems. Many alcoholics will repeat unsuccessful attempts at abstaining, developing a pattern of repeated drinking and withdrawal. We investigated whether aberrant histone acetylation contributes to mitochondrial and cellular damage induced by repeated ethanol withdrawal (EW). We also investigated whether this effect of histone acetylation involves let-7f, a small noncoding RNA (microRNA). Male rats received two cycles of an ethanol/control diet (7.5%, 4 weeks) and withdrawal. Their prefrontal cortex was collected to measure the mitochondrial respiration and histone acetylation using extracellular flux (XF) real-time respirometry and gold immunostaining, respectively. Separately, HT22 (mouse hippocampal) cells received two cycles of ethanol exposure (100 mM, 20 hours) and withdrawal. Trichostatin A (TSA) as a histone acetylation promoter and let-7f antagomir were applied during withdrawal. The mitochondrial respiration, let-7f level, and cell viability were assessed using XF respirometry, quantitative polymerase chain reaction, TaqMan let-7f primers, and a calcein-acetoxymethyl assay, respectively. Repeated ethanol withdrawn rats showed a more than 2-fold increase in histone acetylation, accompanied by mitochondrial respiratory suppression. EW-induced mitochondrial respiratory suppression was exacerbated by TSA treatment in a manner that was attenuated by let-7f antagomir cotreatment. TSA treatment did not alter the increasing effect of EW on the let-7f level but dramatically exacerbated the cell death induced by EW. These data suggest that the multiple episodes of withdrawal from chronic ethanol impede mitochondrial and cellular integrity through upregulating histone acetylation, independent of or additively with let-7f.

show abstract

“…For instance, exposure of pubertal male rats to cannabioid leads to long-term changes in gene H3K9 methylation thereby dysregulating the proenkephalin system in the nucleus accumbens (Tomasiewicz et al, 2012). Pubertal exposure to alcohol has been shown to lead to long-term changes in histone acetylation and related gene expression in the rat prefrontal cortex (Pascual et al, 2012). Thus, while recent data have shown epigenetic regulation of puberty at the hypothalamic level, the epigenetic effects of environmental factors on the hypothalamic regulation of puberty are still to be discovered.…”

Section: Genetic Regulation Of Pubertal Timing and Environmental Intementioning

confidence: 99%

Developmental variations in environmental influences including endocrine disruptors on pubertal timing and neuroendocrine control: Revision of human observations and mechanistic insight from rodents

Parent

Franssen

Fudvoye

et al. 2015

Frontiers in Neuroendocrinology

155

140

View full text Add to dashboard Cite

Puberty presents remarkable individual differences in timing reaching over 5 years in humans. We put emphasis on the two edges of the age distribution of pubertal signs in humans and point to an extended distribution towards earliness for initial pubertal stages and towards lateness for final pubertal stages. Such distortion of distribution is a recent phenomenon. This suggests changing environmental influences including the possible role of nutrition, stress and endocrine disruptors. Our ability to assess neuroendocrine effects and mechanisms is very limited in humans. Using the rodent as a model, we examine the impact of environmental factors on the individual variations in pubertal timing and the possible underlying mechanisms. The capacity of environmental factors to shape functioning of the neuroendocrine system is thought to be maximal during fetal and early postnatal life and possibly less important when approaching the time of onset of puberty.

show abstract

Changes in histone acetylation in the prefrontal cortex of ethanol-exposed adolescent rats are associated with ethanol-induced place conditioning

Cited by 116 publications

References 47 publications

All-Trans Retinoic Acid and Sodium Butyrate Enhance Natriuretic Peptide Receptor A Gene Transcription: Role of Histone Modification

All-Trans Retinoic Acid and Sodium Butyrate Enhance Natriuretic Peptide Receptor A Gene Transcription: Role of Histone Modification

Aberrant Histone Acetylation Promotes Mitochondrial Respiratory Suppression in the Brain of Alcoholic Rats

Developmental variations in environmental influences including endocrine disruptors on pubertal timing and neuroendocrine control: Revision of human observations and mechanistic insight from rodents

Contact Info

Product

Resources

About