Oligodendrocyte morphometry and expression of myelin - Related mRNA in ventral prefrontal white matter in major depressive disorder.
Oligodendrocyte morphometry and expression of myelin - Related mRNA in ventral prefrontal white matter in major depressive disorder.
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DOI：
10.1016/j.jpsychires.2015.04.010
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发表时间：
2015-06
影响因子：
4.8
通讯作者：
Newton SS
中科院分区：
文献类型：
--
作者：
Rajkowska G;Mahajan G;Maciag D;Sathyanesan M;Iyo AH;Moulana M;Kyle PB;Woolverton WL;Miguel-Hidalgo JJ;Stockmeier CA;Newton SS
弥散张量成像 (DTI) 已注意到重度抑郁症 (MDD) 中腹侧前额皮质 (vPFC) 的白质紊乱。然而，MDD 中前额叶白质的细胞和分子病理学以及抗抑郁药物的潜在影响尚未完全了解。在MDD的vPFC白质中检查了少突胶质细胞形态测量以及髓磷脂相关的mRNA和蛋白表达。从 20 名 MDD 受试者和 16 名对照受试者身上采集了 vPFC 的深部和回旋白质切片。使用 3 维细胞计数估计 CNPase 免疫反应性 (−IR) 少突胶质细胞的密度和大小。虽然深部白质中少突胶质细胞的密度和胞体大小均未受到显着影响，但 MDD 中回旋白质中的胞体大小显着减小。在长期用氟西汀治疗的恒河猴中，对少突胶质细胞形态测量没有显着影响。使用定量 RTPCR 测量少突胶质细胞相关 mRNA 的 CNPase、PLP1、MBP、MOG、MOBP、Olig1 和 Olig2，MDD 中 PLP1 mRNA 的表达显着降低（与较小的尺寸呈正相关），而 CNPase、OLIG1 和 MOG 的 mRNA 表达增加。 MDD中CNPase蛋白的表达显着降低。四种髓磷脂基因和 CNPase 蛋白表达的改变提示了 MDD 中皮质轴突退化和少突胶质细胞成熟功能障碍的机制。 DTI 揭示，脑回白质中少突胶质细胞形态的变化可能与轴突完整性的改变平行。
White matter disturbance in the ventral prefrontal cortex (vPFC) in major depressive disorder (MDD) has been noted with diffusion tensor imaging (DTI). However, the cellular and molecular pathology of prefrontal white matter in MDD and potential influence of antidepressant medications is not fully understood. Oligodendrocyte morphometry and myelin-related mRNA and protein expression was examined in the white matter of the vPFC in MDD. Sections of deep and gyral white matter from the vPFC were collected from 20 subjects with MDD and 16 control subjects. Density and size of CNPase-immunoreactive (−IR) oligodendrocytes were estimated using 3-dimensional cell counting. While neither density nor soma size of oligodendrocytes was significantly affected in deep white matter, soma size was significantly decreased in the gyral white matter in MDD. In rhesus monkeys treated chronically with fluoxetine there was no significant effect on oligodendrocyte morphometry. Using quantitative RTPCR to measure oligodendrocyte-related mRNA for CNPase, PLP1, MBP, MOG, MOBP, Olig1 and Olig2, in MDD there was a significantly reduced expression of PLP1 mRNA (which positively correlated with smaller sizes) and increased expression of mRNA for CNPase, OLIG1 and MOG. The expression of CNPase protein was significantly decreased in MDD. Altered expression of four myelin genes and CNPase protein suggests a mechanism for the degeneration of cortical axons and dysfunctional maturation of oligodendrocytes in MDD. The change in oligodendrocyte morphology in gyral white matter may parallel altered axonal integrity as revealed by DTI.