Effect of chronic antipsychotic exposure on astrocyte and oligodendrocyte numbers in macaque monkeys
Effect of chronic antipsychotic exposure on astrocyte and oligodendrocyte numbers in macaque monkeys
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DOI：
10.1016/j.biopsych.2007.08.018
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发表时间：
2008-04-15
影响因子：
10.6
通讯作者：
Lewis, David A.
中科院分区：
文献类型：
--
作者：
Konopaske, Glenn T.;Dorph-Petersen, Karl-Anton;Lewis, David A.
背景：体内和死后的研究都表明，精神分裂症患者存在少突胶质细胞和髓鞘改变。然而，目前尚不清楚长期服用抗精神病药物是否会导致这些障碍。我们最近报道，猕猴长期暴露于氟哌啶醇或奥氮平与顶叶灰质神经胶质细胞数量减少10%-18%有关。因此，在这项研究中，我们试图确定较少的胶质细胞数量是否由于较少的少突胶质细胞而不是较少的星形胶质细胞所致。方法：使用荧光免疫细胞化学技术，我们优化了整个组织切片中每种细胞类型的可视化，同时最小化了最终的组织收缩。结果：我们用光学分离器方法对顶叶灰质中的少突胶质细胞总数和星形胶质细胞数量进行了稳健的体视学估计。结果：我们发现，在服用抗精神病药物的猴子中，星形胶质细胞数量显著减少了20.5%，而少突胶质细胞数量没有显著减少12.9%。氟哌啶醇组和奥氮平组也有类似的效果。结论：这些发现表明，研究精神分裂症神经胶质细胞的变化必须考虑抗精神病药物治疗的影响。
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 immunocytochernical 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.