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

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.

Figures

Figure 1

Epifluorescent photomicrographs of CNP-IR oligodendrocytes. Panel A: Low-power (20X) photomicrograph demonstrating the distribution of CNP-IR oligodendrocytes in the superficial cortical layers of the parietal lobe. Dashed line indicates the layer 1−2 border. Calibration bar = 150 μm. Panels B & C: High power (100X) photomicrographs demonstrating typical somal morphology of CNP-IR oligodendrocytes. Calibration bar = 10 μm.

Figure 2

Epifluorescent photomicrographs of S100B-IR astrocytes. Panel A: Low-power (20X) photomicrograph demonstrating the distribution of S100B-IR astrocytes in the superficial cortical layers of the parietal lobe. Dashed line indicates the layer 1−2 border. Calibration bar = 150 μm. Panels B & C: High power (100X) photomicrographs demonstrating typical somal morphology of S100B-IR astrocytes. Calibration bar = 10 μm.

Figure 3

CNP-IR oligodendrocyte cell number, density, and CNP-IR oligodendrocyte number : total glial cell number ratio from the left parietal lobe of the haloperidol- (thin open circles), olanzapine- (thick open circles), and sham- (filled circles) exposed monkeys. No significant differences were detected between groups. The horizontal bars indicate sham and antipsychotic-exposed group means.

Figure 4

S100B-IR astrocyte cell number, density, and S100B-IR astrocyte number : total glial cell number ratio from the left parietal lobe of the haloperidol- (thin open circles), olanzapine- (thick open circles), and sham- (filled circles) exposed monkeys. The number of S100B-IR astrocytes significantly differed between the antipsychotic-exposed and sham groups (p = 0.034). The horizontal bars indicate sham and antipsychotic-exposed group means.