Substance-specific and shared transcription and epigenetic changes in the human hippocampus chronically exposed to cocaine and alcohol

Zhifeng Zhou, Qiaoping Yuan, Deborah C. Mash, David Goldman

Research output: Contribution to journalArticlepeer-review

136 Scopus citations

Abstract

The hippocampus is a key brain region involved in both short- and long-term memory processes and may play critical roles in drug-associated learning and addiction. Using wholegenome sequencing of mRNA transcripts (RNA-Seq) and immunoprecipitation-enriched genomic DNA (ChIP-Seq) coupled with histone H3 lysine 4 trimethylation (H3K4me3), we found extensive hippocampal gene expression changes common to both cocaine-addicted and alcoholic individuals that may reflect neuronal adaptations common to both addictions. However, we also observed functional changes that were related only to long-term cocaine exposure, particularly the inhibition of mitochondrial inner membrane functions related to oxidative phosphorylation and energy metabolism, which has also been observed previously in neurodegenerative diseases. Cocaine-and alcohol-related histone H3K4me3 changes highly overlapped, but greater effects were detected under cocaine exposure. There was no direct correlation, however, between either cocaine- or alcohol- related histone H3k4me3 and gene expression changes at an individual gene level, indicating that transcriptional regulation as well as drug-related gene expression changes are outcomes of a complex gene-regulatory process that includes multifaceted histone modifications.

Original languageEnglish (US)
Pages (from-to)6626-6631
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number16
DOIs
StatePublished - Apr 19 2011

Keywords

  • Drug addiction
  • Histone methylation

ASJC Scopus subject areas

  • General

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