Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran.
Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran.
Brain Res Bull. 2019 Apr;147:174-182. doi: 10.1016/j.brainresbull.2019.01.020. Epub 2019 Feb 6.
The role of endoplasmic reticulum (ER) stress has been proposed in several neurodegenerative and autoimmune diseases and may contribute to neural apoptosis. The complex role of ER stress-mediated apoptosis introduces a novel angle on multiple sclerosis (MS) research. Nevertheless, the mechanisms through which ER stress intermediates apoptosis are not entirely understood. To this aim, we examined the expression of C/EBP homologous protein (CHOP), caspase-12, and protein disulfide isomerase (PDI) in mice with experimental autoimmune encephalomyelitis (EAE). We found the upregulated expression of CHOP, caspase-12, and PDI in the brain of EAE mice in comparison to healthy mice. Furthermore, immunofluorescent dual-label staining verified elevated levels of caspase-12/CHOP in astrocytes, oligodendrocytes, and microglia in the hippocampus section of EAE mice. This study highlighted the presence of ER stress and increased activation of caspase-12 in the hippocampus of mice in response to EAE induction. Higher levels of caspase-12/CHOP in hippocampal oligodendrocytes as compared with microglia and astrocytes denote that oligodendrocytes are particularly sensitive to ER-mediated apoptosis. In conclusion, the regulation of ER stress pathway would be beneficial for the survival of oligodendrocyte.
内质网（ER）应激在几种神经退行性和自身免疫性疾病中起作用，可能导致神经细胞凋亡。ER 应激介导线粒体凋亡的复杂作用为多发性硬化症（MS）研究提供了一个新的角度。然而，ER 应激介导凋亡的机制尚不完全清楚。为此，我们检测了实验性自身免疫性脑脊髓炎（EAE）小鼠中 C/EBP 同源蛋白（CHOP）、半胱天冬酶-12 和蛋白二硫键异构酶（PDI）的表达。与健康小鼠相比，我们发现 EAE 小鼠大脑中 CHOP、半胱天冬酶-12 和 PDI 的表达上调。此外，免疫荧光双重标记染色证实 EAE 小鼠海马区的小胶质细胞、少突胶质细胞和星形胶质细胞中 caspase-12/CHOP 水平升高。这项研究强调了内质网应激的存在以及 EAE 诱导后小鼠海马体中 caspase-12 的激活增加。与小胶质细胞和星形胶质细胞相比，海马体中少突胶质细胞中 caspase-12/CHOP 水平较高，这表明少突胶质细胞对 ER 介导的凋亡特别敏感。总之，内质网应激途径的调节有利于少突胶质细胞的存活。
