Histone Modifications at Gene Promoter Regions in Rat Hippocampus after Acute and Chronic Electroconvulsive Seizures

Abstract

The mechanism of action of electroconvulsive seizures (ECS), one of the most effective treatments of major depression, may involve the regulation of gene expression. Chromatin remodeling at gene promoter regions is increasingly recognized as a key control point of gene expression and may, therefore, partly mediate acute and chronic effects of ECS on gene activity. Here, we assayed how posttranslational modifications of histones, a major form of chromatin remodeling, are altered at several gene promoters in rat hippocampus at 30 min, 2 hr, and 24 hr after acute or repeated ECS. We performed chromatin immunoprecipitation assays to measure levels of histone H3 and H4 acetylation and phosphoacetylation at the promoters of the c-fos, BDNF, and CREB (cAMP response element-binding protein) genes, the expression of which is altered by ECS. We found that, with few exceptions, levels of H4 acetylation correlated with mRNA levels for c-fos, BDNF, and CREB throughout the acute and chronic time course study, whereas acetylation and phosphoacetylation of H3 were detected more selectively. Our findings suggest that the chronic downregulation of c-fos transcription, observed in this study, may be achieved at the level of H4 acetylation, whereas chronic upregulation of BDNF transcription may be sustained via control of H3 acetylation, selectively at the BDNF P3 and P4 promoters. These data provide the first in vivo demonstration of the involvement of chromatin remodeling in ECS-induced regulation of gene expression in the brain and will help in understanding the mechanisms underlying the efficacy of ECS in the treatment of depression.

Region-specific transcriptional changes following the three antidepressant treatments electro convulsive therapy, sleep deprivation and fluoxetine

“…52 The mechanisms mediating such changes may include chromatin remodeling through histone modification as recently demonstrated in a chronic model of ECT. 53 When comparing the three treatments, ECT and SD affect transcription more robustly in the LC than does FLX. This is partly explained by the selectivity of FLX, a serotonin reuptake blocker that can affect the serotonergic projections that are not the most important drivers of neuronal activity for the noradrenergic cells in the LC.…”

Persistent Alterations in Mesolimbic Gene Expression with Abstinence from Cocaine Self-Administration

“…Chromatin immunoprecipitation (ChIP) experiments were performed similarly to those described previously by Nestler and colleagues (Kumar et al, 2005;Tsankova et al, 2004) and as directed by the manufacturer of the ChiP Assay Kit (Upstate Biotechnology, catalog no. 17-245).…”

Epigenetic Regulation of BDNF Expression via the Scaffolding Protein RACK1

“…For example, exon IV is the major contributor to neuronal activity-dependent BDNF expression (33), and significant increases in the expression of the BDNF IV were observed in the amygdala and hippocampus of rats that had experienced a fear-conditioning paradigm (34,35), whereas the level of BDNF exons I and VI are up-regulated in the hippocampus of rats 2 h after context exposure (34). Electroconvulsive seizures lead to increases in the expression of BDNF exon II, as well as exon VI, in rat hippocampus (37), and differential expression of BDNF exons was also found during different periods of prefrontal cortex development (38).…”