Munshi Soumyabrata, Alarbi Ahlam, Zheng Haixia, Kuplicki Rayus, Burrows Kaiping, Figueroa-Hall Leandra, Victor Teresa, Aupperle Robin, Khalsa Sahib, Paulus Martin, Teague T Kent, Savitz Jonathan
Laureate Institute for Brain Research.
Laureate Institute for Brain Research, Tulsa, USA.
Res Sq. 2024 Jan 12:rs.3.rs-3564760. doi: 10.21203/rs.3.rs-3564760/v1.
A subset of major depressive disorder (MDD) is characterized by immune system dysfunction, but the intracellular origin of these immune changes remains unclear. Here we tested the hypothesis that abnormalities in the endoplasmic reticulum (ER) stress, inflammasome activity and mitochondrial biogenesis contribute to the development of systemic inflammation in MDD. RT-qPCR was used to measure mRNA expression of key organellar genes from peripheral blood mononuclear cells (PBMCs) isolated from 186 MDD and 67 healthy control (HC) subjects. The comparative CT (2) method was applied to quantify mRNA expression using as the reference gene. After controlling for age, sex, BMI, and medication status using linear regression models, expression of the inflammasome ( and ) and the ER stress (, , and ) genes was found to be significantly increased in the MDD versus the HC group. After excluding outliers, expression of the inflammasome genes was no longer statistically significant but expression of the ER stress genes (, , and ) and the mitochondrial biogenesis gene, , was significantly increased in the MDD group. and were positively correlated with serum C-reactive protein concentrations. The altered expression of inflammasome activation, ER stress, and mitochondrial biogenesis pathway components suggest that dysfunction of these organelles may play a role in the pathogenesis of MDD.
重度抑郁症（MDD）的一个亚组具有免疫系统功能障碍的特征，但这些免疫变化的细胞内起源仍不清楚。在这里，我们检验了以下假设：内质网（ER）应激、炎性小体活性和线粒体生物发生异常导致MDD患者全身炎症的发生。采用逆转录定量聚合酶链反应（RT-qPCR）检测了186例MDD患者和67例健康对照（HC）受试者外周血单个核细胞（PBMC）中关键细胞器基因的mRNA表达。采用比较CT（2）法，以 为参照基因定量mRNA表达。使用线性回归模型控制年龄、性别、体重指数和用药状态后，发现MDD组炎性小体（ 和 ）和ER应激（ 、 和 ）基因的表达显著高于HC组。排除异常值后，炎性小体基因的表达不再具有统计学意义，但MDD组ER应激基因（ 、 和 ）和线粒体生物发生基因 的表达显著增加。 和 与血清C反应蛋白浓度呈正相关。炎性小体激活、ER应激和线粒体生物发生途径成分的表达改变表明，这些细胞器的功能障碍可能在MDD的发病机制中起作用。
