Department of Psychiatry, McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Montreal, QC, Canada.
CNRS, INT, Institute Neuroscience Timone, Aix-Marseille Université, Marseille, France.
Sci Rep. 2024 Apr 9;14(1):8258. doi: 10.1038/s41598-024-58278-2.
Major depressive disorder (MDD) is a complex and potentially debilitating illness whose etiology and pathology remains unclear. Non-coding RNAs have been implicated in MDD, where they display differential expression in the brain and the periphery. In this study, we quantified small nucleolar RNA (snoRNA) expression by small RNA sequencing in the lateral habenula (LHb) of individuals with MDD (n = 15) and psychiatrically-healthy controls (n = 15). We uncovered five snoRNAs that exhibited differential expression between MDD and controls (FDR < 0.01). Specifically, SNORA69 showed increased expression in MDD and was technically validated via RT-qPCR. We further investigated the expression of Snora69 in the LHb and peripheral blood of an unpredicted chronic mild stress (UCMS) mouse model of depression. Snora69 was specifically up-regulated in mice that underwent the UCMS paradigm. SNORA69 is known to guide pseudouridylation onto 5.8S and 18S rRNAs. We quantified the relative abundance of pseudouridines on 5.8S and 18S rRNA in human post-mortem LHb samples and found increased abundance of pseudouridines in the MDD group. Overall, our findings indicate the importance of brain snoRNAs in the pathology of MDD. Future studies characterizing SNORA69's role in MDD pathology is warranted.
重度抑郁症（MDD）是一种复杂且可能使人衰弱的疾病，其病因和发病机制仍不清楚。非编码 RNA 与 MDD 有关，它们在大脑和外周组织中表现出差异表达。在这项研究中，我们通过小 RNA 测序定量了 MDD 患者（n=15）和精神健康对照组（n=15）外侧缰核（LHb）中的小核仁 RNA（snoRNA）表达。我们发现了五个在 MDD 和对照组之间表现出差异表达的 snoRNA（FDR<0.01）。具体来说，SNORA69 在 MDD 中表达增加，并通过 RT-qPCR 进行了技术验证。我们进一步研究了未预测的慢性轻度应激（UCMS）抑郁小鼠模型中 LHb 和外周血中 Snora69 的表达。Snora69 在接受 UCMS 范式的小鼠中特异性上调。SNORA69 已知可指导假尿嘧啶化到 5.8S 和 18S rRNA 上。我们定量了人死后 LHb 样本中 5.8S 和 18S rRNA 上假尿嘧啶的相对丰度，发现 MDD 组的假尿嘧啶丰度增加。总的来说，我们的研究结果表明脑 snoRNA 在 MDD 病理中的重要性。未来研究表征 SNORA69 在 MDD 病理中的作用是必要的。
