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. 2004 Mar;88(5):1211-9.
doi: 10.1046/j.1471-4159.2003.02247.x.

Gene expression profile of the nucleus accumbens of human cocaine abusers: evidence for dysregulation of myelin

Dawn N Albertson  1 , Barb Pruetz, Carl J Schmidt, Donald M Kuhn, Gregory Kapatos, Michael J Bannon
Affiliations

Gene expression profile of the nucleus accumbens of human cocaine abusers: evidence for dysregulation of myelin

Dawn N Albertson et al. J Neurochem. 2004 Mar.

Abstract

Chronic cocaine abuse induces long-term neural adaptations as a consequence of alterations in gene expression. This study was undertaken to identify those transcripts differentially regulated in the nucleus accumbens of human cocaine abusers. Affymetrix microarrays were used to measure transcript abundance in 10 cocaine abusers and 10 control subjects matched for age, race, sex, and brain pH. As expected, gene expression of cocaine- and amphetamine-regulated transcript (CART) was increased in the nucleus accumbens of cocaine abusers. The most robust and consistent finding, however, was a decrease in the expression of a number of myelin-related genes, including myelin basic protein (MBP), proteolipid protein (PLP), and myelin-associated oligodendrocyte basic protein (MOBP). The differential expression seen by microarray for CART as well as MBP, MOBP, and PLP was verified by RT-PCR. In addition, immunohistochemical experiments revealed a decrease in the number of MBP-immunoreactive oligodendrocytes present in the nucleus accumbens and surrounding white matter of cocaine abusers. These findings suggest a dysregulation of myelin in human cocaine abusers.

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Figures

Fig. 1
Fig. 1
Decreased expression of myelin-related genes in cocaine users. Transcript abundance was determined by both microarray (■) and quantitative real-time RT–PCR (□, RT–PCR) for (a) myelin basic protein (MBP), (b) myelin-associated oligodendrocyte basic protein (MOBP), and (c) proteolipid protein (PLP) as describe in Materials and methods. The MBP microarray data are averaged values from two independent representations of MBP on the array.
Fig. 2
Fig. 2
Decreased abundance of MBP-immunoreactive oligodendrocytes in cocaine abusers’ nucleus accumbens. (a) High magnification view of a single MBP-positive oligodendrocyte counterstained with cre-syl violet. Note the contact with an MBP-positive fiber bundle in the left-hand portion of the figure. MBP-positive oligodendrocytes (indicated by arrows) were evident throughout the gray matter and fiber bundles of control subjects (b and d, respectively) but were rarely seen in the nucleus accumbens of matched cocaine abusers (c and e, respectively).
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