Bioinformatics Multidisciplinary Environment, Federal University of Rio Grande do Norte Brazil.
Bioinformatics Multidisciplinary Environment, Federal University of Rio Grande do Norte Brazil.
Neuroscience. 2024 Nov 1;559:272-282. doi: 10.1016/j.neuroscience.2024.09.012. Epub 2024 Sep 14.
Major depressive disorder (MDD) is a leading global cause of disability, being more prevalent in females, possibly due to molecular and neuronal pathway differences between females and males. However, the connection between transcriptional changes and MDD remains unclear. We identified transcriptionally altered genes (TAGs) in MDD through gene and transcript expression analyses, focusing on sex-specific differences. Analyzing 263 brain samples from both sexes, we conducted differential gene expression, differential transcript expression, and differential transcript usage analyses, revealing 1169 unique TAGs, primarily in the prefrontal areas, with nearly half exhibiting transcript-level alterations. Females showed notable RNA splicing and export process disruptions in the orbitofrontal cortex, alongside altered DDX39B gene expression in five of the six brain regions in both sexes. Our findings suggest that disruptions in RNA processing pathways may play a vital role in MDD.
重度抑郁症（MDD）是全球主要的致残原因，女性的发病率更高，这可能是由于女性和男性之间的分子和神经元途径存在差异。然而，转录变化与 MDD 之间的联系仍不清楚。我们通过基因和转录本表达分析鉴定了 MDD 中的转录改变基因（TAGs），重点关注性别特异性差异。我们分析了来自两性的 263 个大脑样本，进行了差异基因表达、差异转录本表达和差异转录本使用分析，发现了 1169 个独特的 TAGs，主要在前额区域，其中近一半表现出转录水平的改变。女性在眶额皮质中表现出明显的 RNA 剪接和输出过程中断，以及两性六个脑区中的五个脑区 DDX39B 基因表达改变。我们的研究结果表明，RNA 处理途径的中断可能在 MDD 中起着至关重要的作用。
