Downregulation of oligodendrocyte transcripts is associated with impaired prefrontal cortex function in rats

SCHIZOPHRENIA RESEARCH

卷:113

Article

Gregg, Justin R.^1,2  Herring, Nicole R.^1,2  Naydenov, Alipi V.^1,2  Hanlin, Ryan P.^1,2  Konradi, Christine^1,2,3,4 

[1] Vanderbilt Univ, Dept Pharmacol, Nashville, TN 37232 USA

[2] Vanderbilt Univ, Dept Psychiat, Nashville, TN 37232 USA

[3] Vanderbilt Univ, Ctr Mol Neurosci, Nashville, TN 37232 USA

[4] Vanderbilt Univ, Kennedy Ctr Res Human Dev, Nashville, TN 37232 USA

关键词: Oligodendrocytes;    Attentional set-shifting task;    Prefrontal cortex;    Hippocampus;    Schizophrenia;    Adolescence;   

DOI  :  10.1016/j.schres.2009.05.023

来源: Elsevier

【 摘 要 】

Abnormalities of brain white matter and oligodendroglia are among the most consistent findings in schizophrenia (Sz) research. Various gene expression microarray studies of postmortem Sz brains showed a downregulation of myelin transcripts, while imaging and microscopy studies demonstrated decreases in prefrontal cortical (PFC) white matter volume and oligodendroglia density. Currently, the extent to which reduced oligodendrocyte markets contribute to pathophysiological domains of Sz is unknown. We exposed adolescent rats to cuprizone (CPZ), a copper chelator known to cause demyelination in mice, and examined expression of oligodendrocyte mRNA transcripts and PFC-mediated behavior. Rats on the CPZ diet showed decreased expression of mRNA transcripts encoding oligodendroglial proteins within the medial PFC, but not in the hippocampus or the striatum. These rats also displayed a specific deficit in the ability to shift between perceptual dimensions in the attentional set-shifting task, a PFC-mediated behavioral paradigm modeled after the Wisconsin Card Sorting Test (WCST). The inability to shift strategies corresponds to the deficits exhibited by Sz patients in the WCST. The results demonstrate that a reduction in oligodendrocyte markers is associated with impaired PFC-mediated behaviors. Thus, CPZ exposure of rats can serve as a model to examine the contribution of oligodendrocyte perturbation to cognitive deficits observed in Sz. (C) 2009 Elsevier B.V. All rights reserved.

【 授权许可】

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