Garcia Jon Patrick T, Tayo Lemmuel L
School of Chemical, Biological, and Materials Engineering and Sciences, Mapúa University, Manila 1002, Philippines.
School of Graduate Studies, Mapúa University, Manila 1002, Philippines.
Biology (Basel). 2024 Sep 30;13(10):787. doi: 10.3390/biology13100787.
Bipolar disorder (BPD) is a serious psychiatric condition that is characterized by the frequent shifting of mood patterns, ranging from manic to depressive episodes. Although there are already treatment strategies that aim at regulating the manifestations of this disorder, its etiology remains unclear and continues to be a question of interest within the scientific community. The development of RNA sequencing techniques has provided newer and better approaches to studying disorders at the transcriptomic level. Hence, using RNA-seq data, we employed intramodular connectivity analysis and network pharmacology assessment of disease-associated variants to elucidate the biological pathways underlying the complex nature of BPD. This study was intended to characterize the expression profiles obtained from three regions in the brain, which are the nucleus accumbens (nAcc), the anterior cingulate cortex (AnCg), and the dorsolateral prefrontal cortex (DLPFC), provide insights into the specific roles of these regions in the onset of the disorder, and present potential targets for drug design and development. The nAcc was found to be highly associated with genes responsible for the deregulated transcription of neurotransmitters, while the DLPFC was greatly correlated with genes involved in the impairment of components crucial in neurotransmission. The AnCg did show association with some of the expressions, but the relationship was not as strong as the other two regions. Furthermore, disease-associated variants or single nucleotide polymorphisms (SNPs) were identified among the significant genes in BPD, which suggests the genetic interrelatedness of such a disorder and other mental illnesses. , , and were the genes with disease-associated variants expressed in the nAcc; and were the genes with disease-associated variants expressed in the AnCg; and , , , , and were the genes with disease-associated variants expressed in the DLPFC. Aside from unraveling the molecular and cellular mechanisms behind the expression of BPD, this investigation was envisioned to propose a new research pipeline in studying the transcriptome of psychiatric disorders to support and improve existing studies.
双相情感障碍（BPD）是一种严重的精神疾病，其特征是情绪模式频繁波动，从躁狂发作到抑郁发作不等。尽管已经有旨在调节这种疾病表现的治疗策略，但其病因仍不清楚，并且仍然是科学界感兴趣的问题。RNA测序技术的发展为在转录组水平研究疾病提供了更新更好的方法。因此，我们利用RNA测序数据，采用模块内连通性分析和疾病相关变异的网络药理学评估，以阐明BPD复杂本质背后的生物学途径。本研究旨在表征从大脑三个区域获得的表达谱，这三个区域分别是伏隔核（nAcc）、前扣带回皮质（AnCg）和背外侧前额叶皮质（DLPFC），深入了解这些区域在该疾病发病过程中的具体作用，并提出药物设计和开发的潜在靶点。研究发现，伏隔核与负责神经递质转录失调的基因高度相关，而背外侧前额叶皮质与参与神经传递中关键成分受损的基因密切相关。前扣带回皮质确实与一些表达存在关联，但其关系不如其他两个区域那么强烈。此外，在双相情感障碍的重要基因中鉴定出了疾病相关变异或单核苷酸多态性（SNP），这表明这种疾病与其他精神疾病存在遗传相关性。 、 和 是在伏隔核中表达的具有疾病相关变异的基因； 和 是在前扣带回皮质中表达的具有疾病相关变异的基因； 、 、 、 和 是在背外侧前额叶皮质中表达的具有疾病相关变异的基因。除了解开双相情感障碍表达背后的分子和细胞机制外，本研究还设想提出一种研究精神疾病转录组的新研究途径，以支持和改进现有研究。
