Altered Expression of Endoplasmic Reticulum Stress-Related Genes in the Middle Frontal Cortex of Subjects with Autism Spectrum Disorder.
Altered Expression of Endoplasmic Reticulum Stress-Related Genes in the Middle Frontal Cortex of Subjects with Autism Spectrum Disorder.
复制标题
DOI：
10.1159/000477212
复制
发表时间：
2017-11-01
期刊：
影响因子：
--
通讯作者：
Pillai, Anilkumar
中科院分区：
文献类型：
--
作者：
Crider, Amanda;Ahmed, Anthony O;Pillai, Anilkumar
内质网（ER）是一种重要的细胞器，负责蛋白质的折叠和分选。ER稳态的紊乱可以触发称为未折叠蛋白质反应的细胞反应，导致未折叠或错误折叠蛋白质在ER腔中积累，称为ER应激。最近的一些研究表明，自闭症谱系障碍（ASD）易感突触基因的突变诱导ER应激。然而，目前尚不清楚是否ER应激相关基因在ASD受试者的大脑中发生改变。在本研究中，我们研究了ER应激相关基因（ATF 4，ATF 6，PERK，XBP 1，sXBP 1，CHOP和IRE 1）在ASD和对照组的死后额中回的mRNA表达。RT-PCR分析显示ASD受试者额中回ATF 4、ATF 6、PERK、XBP 1、CHOP和IRE 1的mRNA水平显著增加。此外，我们发现ER应激基因的mRNA水平与ASD患者刻板行为的诊断评分显著正相关。这些结果首次提供了ASD患者大脑中ER应激基因失调的证据。
The endoplasmic reticulum (ER) is an important organelle responsible for the folding and sorting of proteins. Disturbances in ER homeostasis can trigger a cellular response known as the unfolded protein response, leading to accumulation of unfolded or misfolded proteins in the ER lumen called ER stress. A number of recent studies suggest that mutations in autism spectrum disorder (ASD)-susceptible synaptic genes induce ER stress. However, it is not known whether ER stress-related genes are altered in the brain of ASD subjects. In the present study, we investigated the mRNA expression of ER stress-related genes (ATF4, ATF6, PERK, XBP1, sXBP1, CHOP, and IRE1) in the postmortem middle frontal gyrus of ASD and control subjects. RT-PCR analysis showed significant increases in the mRNA levels of ATF4, ATF6, PERK, XBP1, CHOP, and IRE1 in the middle frontal gyrus of ASD subjects. In addition, we found a significant positive association of mRNA levels of ER stress genes with the diagnostic score for stereotyped behavior in ASD subjects. These results, for the first time, provide the evidence of the dysregulation of ER stress genes in the brain of subjects with ASD.