Feature Finding Title
Featured Finding Figure
Both in vivo and post-mortem studies suggest that oligodendrocyte and myelination alterations are present in individuals with schizophrenia. However, it is unclear whether prolonged treatment with antipsychotic medications contributes to these disturbances. We recently reported that chronic exposure of macaque monkeys to haloperidol or olanzapine was associated with a 10-18% lower glial cell number in the parietal grey matter. Consequently, in this study we sought to determine whether the lower glial cell number was due to fewer oligodendrocytes as opposed to lower numbers of astrocytes. Using fluorescent immunocytochemical techniques, we optimized the visualization of oligodendrocytes (left panel) and astrocytes (right panel) throughout the entire thickness of tissue sections, while minimizing final tissue shrinkage. As a result, we were able to obtain robust stereological estimates of total oligodendrocyte and astrocyte numbers in the parietal grey matter using the optical fractionator method. We found a significant 20.5% lower astrocyte number with a non-significant 12.9% lower oligodendrocyte number in the antipsychotic-exposed monkeys. Similar effects were seen in both the haloperidol and olanzapine groups. In summary, the findings of this study indicate that chronic exposure to haloperidol and olanzapine is associated with significantly lower astrocyte number in the parietal cortex. Since fewer astrocytes might impact the synthesis, metabolism, and neurotransmission of cortical glutamate, this study suggests that both in vivo imaging and post-mortem studies of the glutamate system in schizophrenia should control for the possible confounding effect of chronic antipsychotic treatment. In addition, this study illustrates the use of methods which allowed robust and efficient stereological number estimates of immunofluorescently-labeled cells in the CNS and have relevance to experiments conducted in diverse areas of neuroscience.
Konopaske GT, Dorph-Petersen KA, Sweet RA, Pierri J, Zhang W, Sampson A, and Lewis DA: Effect of chronic antipsychotic exposure on astrocyte and oligodendrocyte numbers in macaque monkeys. Biological Psychiatry 63:759-765, 2008.

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David A. Lewis, M.D. | Department of Psychiatry | University of Pittsburgh
3811 O'Hara Street, Biomedical Science Tower W1654
Pittsburgh, Pennsylvania 15213-2593
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