Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2-3
pubmed:dateCreated
2009-8-11
pubmed:abstractText
Abnormalities of brain white matter and oligodendroglia are among the most consistent findings in schizophrenia (Sz) research. Various gene expression microarray studies of post-mortem 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 markers 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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1573-2509
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
113
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
277-87
pubmed:dateRevised
2010-12-3
pubmed:meshHeading
pubmed-meshheading:19570651-Age Factors, pubmed-meshheading:19570651-Animals, pubmed-meshheading:19570651-Attention, pubmed-meshheading:19570651-Body Weight, pubmed-meshheading:19570651-Corpus Striatum, pubmed-meshheading:19570651-Cuprizone, pubmed-meshheading:19570651-Down-Regulation, pubmed-meshheading:19570651-Eating, pubmed-meshheading:19570651-Gene Expression Profiling, pubmed-meshheading:19570651-Hippocampus, pubmed-meshheading:19570651-Locomotion, pubmed-meshheading:19570651-Male, pubmed-meshheading:19570651-Monoamine Oxidase Inhibitors, pubmed-meshheading:19570651-Neuropsychological Tests, pubmed-meshheading:19570651-Oligodendroglia, pubmed-meshheading:19570651-Oligonucleotide Array Sequence Analysis, pubmed-meshheading:19570651-Prefrontal Cortex, pubmed-meshheading:19570651-Rats, pubmed-meshheading:19570651-Rats, Sprague-Dawley, pubmed-meshheading:19570651-Startle Reaction
pubmed:year
2009
pubmed:articleTitle
Downregulation of oligodendrocyte transcripts is associated with impaired prefrontal cortex function in rats.
pubmed:affiliation
Department of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural