Gene Expression in Human Hippocampus from Cocaine Abusers Identifies Genes which Regulate Extracellular Matrix Remodeling

Deborah C Mash, Jarlath Ffrench-Mullen, Nikhil Adi, Yujing Qin, Andrew Buck, John Pablo

Research output: Contribution to journalArticle

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Abstract

The chronic effects of cocaine abuse on brain structure and function are blamed for the inability of most addicts to remain abstinent. Part of the difficulty in preventing relapse is the persisting memory of the intense euphoria or cocaine "rush". Most abused drugs and alcohol induce neuroplastic changes in brain pathways subserving emotion and cognition. Such changes may account for the consolidation and structural reconfiguration of synaptic connections with exposure to cocaine. Adaptive hippocampal plasticity could be related to specific patterns of gene expression with chronic cocaine abuse. Here, we compare gene expression profiles in the human hippocampus from cocaine addicts and age-matched drug-free control subjects. Cocaine abusers had 151 gene transcripts upregulated, while 91 gene transcripts were downregulated. Topping the list of cocaine-regulated transcripts was RECK in the human hippocampus (FC = 2.0; p<0.05). RECK is a membrane-anchored MMP inhibitor that is implicated in the coordinated regulation of extracellular matrix integrity and angiogenesis. In keeping with elevated RECK expression, active MMP9 protein levels were decreased in the hippocampus from cocaine abusers. Pathway analysis identified other genes regulated by cocaine that code for proteins involved in the remodeling of the cytomatrix and synaptic connections and the inhibition of blood vessel proliferation (PCDH8, LAMB1, ITGB6, CTGF and EphB4). The observed microarray phenotype in the human hippocampus identified RECK and other region-specific genes that may promote long-lasting structural changes with repeated cocaine abuse. Extracellular matrix remodeling in the hippocampus may be a persisting effect of chronic abuse that contributes to the compulsive and relapsing nature of cocaine addiction.

Original languageEnglish
Article numbere0001187
JournalPLoS One
Volume2
Issue number11
DOIs
StatePublished - Dec 1 2007

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cocaine
Cocaine
extracellular matrix
Gene expression
Extracellular Matrix
Hippocampus
Genes
Cocaine-Related Disorders
Gene Expression
gene expression
hippocampus
genes
Matrix Metalloproteinase Inhibitors
Drug and Narcotic Control
long term effects
Brain
Transcriptome
Cognition
Blood Vessels
brain

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Gene Expression in Human Hippocampus from Cocaine Abusers Identifies Genes which Regulate Extracellular Matrix Remodeling. / Mash, Deborah C; Ffrench-Mullen, Jarlath; Adi, Nikhil; Qin, Yujing; Buck, Andrew; Pablo, John.

In: PLoS One, Vol. 2, No. 11, e0001187, 01.12.2007.

Research output: Contribution to journalArticle

Mash, Deborah C ; Ffrench-Mullen, Jarlath ; Adi, Nikhil ; Qin, Yujing ; Buck, Andrew ; Pablo, John. / Gene Expression in Human Hippocampus from Cocaine Abusers Identifies Genes which Regulate Extracellular Matrix Remodeling. In: PLoS One. 2007 ; Vol. 2, No. 11.
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