Evidence for morphological alterations in prefrontal white matter glia in schizophrenia and bipolar disorder
Evidence for morphological alterations in prefrontal white matter glia in schizophrenia and bipolar disorder
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DOI：
10.1503/jpn.130277
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发表时间：
2014-11-01
影响因子：
4.3
通讯作者：
Beasley, Clare L.
中科院分区：
文献类型：
--
作者：
Hercher, Christa;Chopra, Vikramjit;Beasley, Clare L.
背景资料：脑成像研究表明，体积减少和受损的白色物质的完整性发生在精神分裂症和双相情感障碍（BD）。然而，细胞相关性尚未确定。为了解决这个问题，我们评估了精神分裂症，BD和非精神病对照样本的死后白色物质中的少突胶质细胞，星形胶质细胞和小胶质细胞群体。研究方法：在死后邻近背外侧前额叶皮质的白色物质中定量表达胶质细胞酸性蛋白（GFAP）的星形胶质细胞和表达离子化钙结合适配分子-1（IBA-1）的小胶质细胞的密度、面积分数和空间分布，以及Nissl染色的少突胶质细胞的密度、核大小和空间分布（Brodmann区9）的水平。此外，通过酶联免疫吸附试验和免疫印迹法对相同样品中的少突胶质细胞相关蛋白髓鞘碱性蛋白和2 '，3'-环-β-核苷酸3 '-磷酸二酯酶（CNX 3）进行定量。结果如下：少突胶质细胞密度（p = 0.012）和CNR蛋白水平（p = 0.038）在组间不同，与对照样品相比，BD中增加。GFAP面积分数（p = 0.05）和星形胶质细胞空间分布（p = 0.040）在组间也不同，反映了精神分裂症和BD样品中面积分数降低和细胞聚集增加。局限性：使用形态学标准鉴定少突胶质细胞。结论：本研究为精神分裂症和BD患者前额叶白色区胶质细胞的病理改变提供了依据。在主要精神疾病中，白色物质中少突胶质细胞和星形胶质细胞数量的变化可能反映了轴突结构或代谢支持的破坏。
Background: Brain imaging studies suggest that volume reductions and compromised white matter integrity occur in schizophrenia and bipolar disorder (BD). However, the cellular correlates have not yet been identified. To address this issue we assessed oligodendrocyte, astrocyte and microglial populations in postmortem white matter from schizophrenia, BD and nonpsychiatric control samples. Methods: The density, areal fraction and spatial distribution of glial fibrillary acidic protein (GFAP)-expressing astrocytes and ionized calcium-binding adaptor molecule-1 (IBA-1)-expressing microglia as well as the density, nuclear size and spatial distribution of Nissl-stained oligodendrocytes were quantified in postmortem white matter adjacent to the dorsolateral prefrontal cortex (Brodmann area 9) in schizophrenia, BD and control samples (n = 20). In addition, the oligodendrocyte-associated proteins myelin basic protein and 2', 3'--cyclic--nucleotide 3'-phosphodiesterase (CNPase) were quantified in the same samples by enzyme-linked immunosorbent assay and immunoblotting. Results: Oligodendrocyte density (p = 0.012) and CNPase protein levels (p = 0.038) differed between groups, being increased in BD compared with control samples. The GFAP area fraction (p = 0.05) and astrocyte spatial distribution (p = 0.040) also differed between groups, reflecting decreased area fraction and increased cell clustering in both schizophrenia and BD samples. Limitations: Oligodendrocytes were identified using morphological criteria. Conclusion: This study provides evidence for glial pathology in prefrontal white matter in schizophrenia and BD. Changes in oligodendrocyte and astrocyte populations in white matter in the major psychiatric disorders may reflect disruptions in structural or metabolic support of axons.