Effect of chronic antipsychotic exposure on astrocyte and oligodendrocyte numbers in macaque monkeys

Biol Psychiatry. 2008 Apr 15;63(8):759-65. doi: 10.1016/j.biopsych.2007.08.018. Epub 2007 Oct 22.

Abstract

Background: Both in vivo and postmortem 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.

Methods: With fluorescent immunocytochemical techniques, we optimized the visualization of each cell type 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 with the optical fractionator method.

Results: 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.

Conclusions: These findings suggest that studies investigating glial cell alterations in schizophrenia must take into account the effect of antipsychotic treatment.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antipsychotic Agents / toxicity*
  • Astrocytes / drug effects*
  • Astrocytes / pathology
  • Benzodiazepines / toxicity*
  • Cell Count
  • Haloperidol / toxicity*
  • Macaca fascicularis
  • Male
  • Olanzapine
  • Oligodendroglia / drug effects*
  • Oligodendroglia / pathology
  • Parietal Lobe / drug effects*
  • Parietal Lobe / pathology

Substances

  • Antipsychotic Agents
  • Benzodiazepines
  • Haloperidol
  • Olanzapine