Substance-specific and shared transcription and epigenetic changes in the human hippocampus chronically exposed to cocaine and alcohol.
paper
Cited
Public
Unavailable
- Authors
- Zhou, Zhifeng; Yuan, Qiaoping; Mash, Deborah C; Goldman, David
- Year
- 2011
- Journal
- Proceedings of the National Academy of Sciences of the United States of America
- PMID
- 21464311
- DOI
- 10.1073/pnas.1018514108
- PMCID
- PMC3081016
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 whole genome 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.
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