Altered glial marker expression in autistic post-mortem prefrontal cortex and cerebellum.
Altered glial marker expression in autistic post-mortem prefrontal cortex and cerebellum.
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DOI：
10.1186/2040-2392-5-3
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发表时间：
2014-01-10
期刊：
影响因子：
6.2
通讯作者：
Rennert OM
中科院分区：
文献类型：
--
作者：
Edmonson C;Ziats MN;Rennert OM
自闭症谱系障碍（ASD）的细胞机制尚未完全了解，但ASD被认为最终是由突触发生中断引起的。然而，研究也表明，自闭症患者死后脑组织中的胶质细胞数量和功能异常。直接评估死后人脑组织中的神经胶质细胞在技术上具有挑战性，限制了人类ASD研究中的神经胶质研究。因此，我们试图确定神经胶质细胞类型特异性标志物是否可以以与已知细胞发现一致的方式在自闭症脑组织中改变，使得它们可以作为神经胶质细胞数量和/或激活模式的代表。我们通过qRT-PCR评估了五种胶质细胞特异性标志物和两种神经元特异性标志物的相对表达。我们研究了9个自闭症患者死后大脑样本和9个神经正常对照的前额叶皮层（PFC）和小脑的组织样本。使用标准化为管家基因β-肌动蛋白的ΔΔCt方法确定基因表达的相对倍数变化，组间双尾Student t检验P <0.05被认为是显著的。星形胶质细胞和小胶质细胞特异性标记物在自闭症PFC中的表达显著高于匹配的对照组，而在自闭症样本中只有小脑中的星形胶质细胞标记物升高。与此相反，神经元特异性标记物在自闭症患者的PFC和小脑中的表达显著低于对照组。这些结果与先前的研究结果一致，显示自闭症死后脑组织中神经胶质细胞数量增加和神经胶质细胞基因表达上调，特别是在PFC中，以及自闭症患者PFC和小脑中神经元数量减少。这些结果与死后自闭症脑组织细胞水平研究的一致性表明，神经胶质细胞类型特异性标志物的表达可能作为一种有用的替代传统的细胞表征方法，特别是当缺乏适当保存的死后组织。此外，这些结果表明自闭症大脑中异常的胶质细胞特异性基因表达，支持先前观察到ASD中胶质细胞数量或激活模式改变的研究。未来的工作应该直接评估细胞类型特异性标志物水平与细胞数量和激活模式之间的相关性。
The cellular mechanism(s) underlying autism spectrum disorders (ASDs) are not completely understood, but ASDs are thought to ultimately result from disrupted synaptogenesis. However, studies have also shown that glial cell numbers and function are abnormal in post-mortem brain tissue from autistic patients. Direct assessment of glial cells in post-mortem human brain tissue is technically challenging, limiting glial research in human ASD studies. Therefore, we attempted to determine if glial cell-type specific markers may be altered in autistic brain tissue in a manner that is consistent with known cellular findings, such that they could serve as a proxy for glial cell numbers and/or activation patterns. We assessed the relative expression of five glial-specific markers and two neuron-specific markers via qRT-PCR. We studied tissue samples from the prefrontal cortex (PFC) and cerebellum of nine post-mortem autistic brain samples and nine neurologically-normal controls. Relative fold-change in gene expression was determined using the ΔΔCt method normalized to housekeeping gene β-actin, with a two-tailed Student’s t-test P <0.05 between groups considered as significant. Both astrocyte- and microglial-specific markers were significantly more highly expressed in autistic PFC as compared to matched controls, while in the cerebellum only astrocyte markers were elevated in autistic samples. In contrast, neuron-specific markers showed significantly lower expression in both the PFC and cerebellum of autistic patients as compared to controls. These results are in line with previous findings showing increased glial cell numbers and up-regulation of glial cell gene expression in autistic post-mortem brain tissue, particularly in the PFC, as well as decreased number of neurons in both the PFC and cerebellum of autistic patients. The concordance of these results with cell-level studies in post-mortem autistic brain tissue suggests that expression of glial cell-type specific markers may serve as a useful alternative to traditional cellular characterization methods, especially when appropriately-preserved post-mortem tissue is lacking. Additionally, these results demonstrate abnormal glial-specific gene expression in autistic brains, supporting previous studies that have observed altered glial cell numbers or activation patterns in ASDs. Future work should directly assess the correlation between cell-type specific marker levels and cell number and activation patterns.
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影响因子：
14.5
作者：
Bailey, A;Luthert, P;Lantos, P
通讯作者：
Lantos, P
DOI：
10.1006/bbrc.1996.1112
发表时间：
1996-07-25
影响因子：
3.1
作者：
Imai, Y;Ibata, I;Kohsaka, S
通讯作者：
Kohsaka, S
通过神经胶质调节突触连通性。
影响因子：
64.8
作者：
Eroglu, Cagla;Barres, Ben A.
通讯作者：
Barres, Ben A.
影响因子：
2.3
作者：
Fatemi, S. Hossein;Folsom, Timothy D.;Reutiman, Teri J.;Lee, Susanne
通讯作者：
Lee, Susanne
影响因子：
6.2
作者：
Anitha A;Nakamura K;Thanseem I;Yamada K;Iwayama Y;Toyota T;Matsuzaki H;Miyachi T;Yamada S;Tsujii M;Tsuchiya KJ;Matsumoto K;Iwata Y;Suzuki K;Ichikawa H;Sugiyama T;Yoshikawa T;Mori N
通讯作者：
Mori N