Expression of Transcripts for Myelin Related Genes in Postmortem Brain from Cocaine Abusers

Abstract

Chronic abuse of cocaine is known to cause neuroadaptive changes in the nucleus accumbens (NAc) and ventral tegmental area (VTA). In addition, altered expression of the myelin-related genes MBP, MOBP, PLP1 as well as of MAL2 in NAc was recently reported by gene array analysis in brains from cocaine abusers. In the present study we used in situ hybridization to quantify transcript expression of these four genes, as well as for the myelin-related transcripts encoding quaking, EDG2, claudin-11, transferrin, CNP, and MAG in caudate, putamen, internal capsule, and NAc in postmortem brain from cocaine abusers and matched comparison subjects. Most transcripts were not different between these groups in these striatal regions, and contrary to previous reports, we did not detect any changes in the NAc. However, expression of the transcript encoding PLP1 was significantly decreased in ventral and dorsal regions of the caudate, putamen, and in the internal capsule. Additionally, expression of claudin-11 and transferrin was decreased in the caudate and internal capsule, respectively. PLP1 is expressed at very high levels in oligodendrocytes and is essential in maintaining stability of myelin sheets. Based on these findings, altered expression of PLP1 in most areas of the striatum suggests that widespread changes to the myelin structure could be associated with the adaptive changes following chronic cocaine abuse.

Regionally-specific alterations in myelin proteins in nonhuman primate white matter following prolonged cocaine self-administration

“…The lack of effects of cocaine self-administration on PLP and MBP gene expression in white matter at the striatal level, although consistent with a study which failed to see MBP or PLP DNA methylation changesin cocaine-exposed rats (Nielsen et al, 2012), was surprising, given the results of previous studies in which these mRNAs were down-regulated in post-mortem studies of human cocaine abusers (Albertson et al, 2004; Bannon et al, 2005; Kristiansen et al, 2009; Lehrmann et al, 2003). These studies focused primarily on transcripts in striatal and prefrontal cortical tissue, however, and although in one report PLP mRNA was altered in the internal capsule (Kristiansen et al, 2009), measurements were not made in samples of callosal or other subcortical white matter, and this difference in the anatomical targets between these two studies and the present investigation may underlie the discrepant findings.…”

Chronic cocaine administration causes extensive white matter damage in brain: Diffusion tensor imaging and immunohistochemistry studies

“…Myelin-related transcripts encoding MBP, cyclic nucleotide 3-phosphodiesterase, MAG, and MOG are decreased following cocaine exposure (Kristiansen et al, 2009). The change in ic was also reported on MRI in cocaine subjects (Lim et al, 2008).…”

Biomarkers for the Development of New Medications for Cocaine Dependence

“…These studies found that the expression of a group of myelin-related genes, including myelin basic protein, proteolipid protein, and myelin-associated oligodentrocyte basic protein was substantially decreased in cocaine abusers in the NAc (Albertson et al, 2004). However, a follow-up study did not find changes in myelin-related gene expression in the NAc, but did find decreased expression of the transcript encoding PLP-1 in the caudate, putamen, and internal capsule (Kristiansen et al, 2009). These findings are consistent with the neuroimaging (ie, DTI) findings of altered white-matter structure in cocaine users discussed above, thus indicating that myelin-related proteins may be a useful toxicity biomarker for future consideration, and illustrate the potential for combining types of biomarkers to aid in mechanistic biomarker discovery.…”