title: Substance-specific and shared transcription and epigenetic changes in the human hippocampus chronically exposed to cocaine and alcohol.
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 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.
authors.affiliation: Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD 20849, USA.
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Zhou
authors.forename: Qiaoping
authors.initials: Q
authors.lastname: Yuan
authors.forename: Deborah C
authors.initials: DC
authors.lastname: Mash
authors.forename: David
authors.initials: D
authors.lastname: Goldman
mesh_terms: D000437:Alcoholism / Q000235:genetics / Q000378:metabolism*; D019970:Cocaine-Related Disorders / Q000235:genetics / Q000378:metabolism*; D044127:Epigenesis, Genetic; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D055106:Genome-Wide Association Study / Q000379:methods; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D008297:Male; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: D009419:Nerve Tissue Proteins