Shared and unique transcriptomic signatures of antidepressant and probiotics action in the mammalian brain

To comprehensively characterize the intrinsic molecular effects of ADs independently of the specifics of particular disease models, we generated 300 transcriptomic profiles from 10 brain regions in naive rats. Three classical tricyclic antidepressants, Bupropion, desipramine, fluoxetine, and a probiotic formulation (Lacidofil®) can massively alter gene expression in most regions [>1,500 differentially expressed genes (DEGs)], suggesting that traditional single-gene or single-pathway analyses may under-represent the complexity of molecular responses. Using spatial transcriptomics in the prefrontal cortex from an independent set of animals, we further delineated DEGs and molecular pathways that exhibited layer-specific differential regulation by probiotics and fluoxetine.为摆脱特定疾病模型的细节限制，全面解析抗抑郁药（antidepressants, ADs）的内在分子效应，我们从10个脑区的未处理正常大鼠中获取了300份转录组谱。本研究选用3种经典三环类抗抑郁药（安非他酮、地昔帕明、氟西汀）与益生菌制剂Lacidofil®，实验发现上述物质可在多数脑区中大幅改变基因表达，涉及超过1500个差异表达基因（differentially expressed genes, DEGs），这提示传统单基因或单通路分析可能低估了分子应答的复杂性。我们通过对独立队列动物的前额叶皮层（prefrontal cortex）开展空间转录组学（spatial transcriptomics）分析，进一步阐明了益生菌与氟西汀可介导层特异性差异调控的差异表达基因及分子通路。