Subcortical oligodendrocyte- and astrocyte-associated gene expression in subjects with schizophrenia, major depression and bipolar disorder
Subcortical oligodendrocyte- and astrocyte-associated gene expression in subjects with schizophrenia, major depression and bipolar disorder
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DOI：
10.1016/j.schres.2009.04.019
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发表时间：
2009-07-01
影响因子：
4.5
通讯作者：
Byne, William
中科院分区：
文献类型：
--
作者：
Barley, Kevin;Dracheva, Stella;Byne, William
在精神分裂症和情感障碍的许多皮层区域中，已经描述了少突胶质细胞和髓鞘基因表达的缺陷;然而，相对较少关注皮层下结构。在这里，我们采用定量真实的时间PCR检测17个基因的mRNA表达的少突胶质细胞前体细胞（OLP）及其衍生物，包括星形胶质细胞。在没有已知精神病史（NC）的受试者（死亡时年龄25-68岁）以及精神分裂症（SZ）、重度抑郁症（MDD）和双相情感障碍（BPD）受试者的尸检材料中，检查了四个皮质下区域（前腹（AV）和丘脑背内侧核（MDN）、内囊（IC）和壳核（Put））。在所有区域的研究中，少突胶质细胞终末分化后表达的基因往往有较低水平的mRNA表达的受试者与SZ相比，NC。这些差异在四个基因（CNP、GALC、MAG和MOG）的区域间具有统计学显著性，并接近TF的显著性。MDD中无基因表达下调。只有TF在BPD和IC中表达不足。相比之下，两个星形胶质细胞相关基因（GFAP和ALDH 1 L1）在所有精神病组中的区域平均表达水平高于NC。相对于NC，SZ和MDD的这些差异达到统计学显著性。年龄与诊断之间无相互作用。大多数的年龄回归有负斜率的少突胶质细胞相关基因的表达。MDN、AV和Put中GFAP的表达与年龄呈显著正相关，而ALDH 1 L1的表达与年龄无关。在所有受试者组中，两种星形胶质细胞基因的表达与除Put外所有区域的累积抗精神病药物暴露高度相关。在某些区域，也观察到神经阻滞剂累积暴露与成熟少突胶质细胞以及双能OLP相关基因的表达之间存在显著正相关。星形胶质细胞基因mRNA表达与终末分化少突胶质细胞基因表达呈多重负相关。这些数据进行了讨论的背景下，髓鞘营业额和精神疾病的潜在影响，以及药物对发展的命运OLPs。由爱思唯尔公司出版
Deficits in the expression of oligodendrocyte and myelin genes have been described in numerous cortical regions in schizophrenia and affective disorders; however, relatively little attention has been paid to subcortical structures. Here we employed quantitative real time PCR to examine the mRNA expression of 17 genes that are expressed by oligodendrocyte precursors (OLPs) and their derivatives, including astrocytes. Four subcortical regions were examined (the anteroventral (AV) and mediodorsal thalamic nuclei (MDN), internal capsule (IC) and putamen (Put)) in postmortem material from subjects (age 25-68 at time of death) with no known psychiatric history (NCs) as well as in subjects with schizophrenia (SZ), major depressive disorder (MDD), and bipolar disorder (BPD). In all regions examined, genes expressed after the terminal differentiation of oligodendrocytes tended to have lower levels of mRNA expression in subjects with SZ compared to NCs. These differences were statistically significant across regions for four genes (CNP, GALC, MAG and MOG) and approached significance for TF. No genes were under expressed in MDD. Only TF was under expressed in BPD and only in the IC. In contrast, two astrocyte-associated genes (GFAP and ALDH1L1) had higher mean expression levels across regions in all psychiatric groups relative to NCs. These differences reached statistical significance for SZ and MDD relative to NCs. There were no age by diagnosis interactions. The majority of age regressions had negative slopes for the expression of oligodendrocyte-associated genes. GFAP but not ALDH1L1 expression was significantly and positively correlated with age in the MDN, AV and Put. Across subject groups the expression of both astrocyte genes was highly correlated with cumulative neuroleptic exposure in all regions except the Put. Significant positive correlations were also observed in some regions between cumulative neuroleptic exposure and the expression of genes associated with mature oligodendrocytes as well as with bipotential OLPs. Multiple negative correlations were observed between the mRNA expression of astrocyte genes and genes expressed by terminally differentiated oligodendrocytes. These data are discussed in the context of myelin turnover and potential effects of psychiatric illness as well as medications on the developmental fate of OLPs. Published by Elsevier B.V.