Depression is a prevalent mental disorder that is associated with aging and contributes to increased mortality and morbidity. The overall prevalence of geriatric depression with clinically significant symptoms is currently on the rise. Recent studies have demonstrated that altered expressions of long non-coding RNAs (lncRNAs) in the brain affect neurodevelopment and manifest modulating functions during the depression. However, most lncRNAs have not yet been studied. Herein, we analyzed the transcriptome of dysregulated lncRNAs to reveal their expressions in a mouse model exhibiting depressive-like behaviors, as well as their corresponding response following antidepressant fluoxetine treatment. A chronic unpredictable mild stress (CUMS) mouse model was applied. A six-week fluoxetine intervention in CUMS-induced mice attenuated depressive-like behaviors. In addition, differential expression analysis of lncRNAs was performed following RNA-sequencing. A total of 282 lncRNAs (134 up-regulated and 148 down-regulated) were differentially expressed in CUMS-induced mice relative to non-stressed counterparts ( P<0.05). Moreover, 370 differentially expressed lncRNAs were identified in CUMS-induced mice after fluoxetine intervention. Gene Ontology (GO) analyses showed an association between significantly dysregulated lncRNAs and protein binding, oxygen binding, and transport activity, while the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that these dysregulated lncRNAs might be involved in inflammatory response pathways. Fluoxetine effectively ameliorated the symptoms of depression in CUMS-induced mice by regulating the expression of lncRNAs in the hippocampus. The findings herein provide valuable insights into the potential mechanism underlying depression in elderly people.
抑郁症是一种与衰老相关的精神障碍疾病，可导致患者发病率和死亡率的增加。目前临床上具有显著抑郁症状的老年抑郁症患者的发病率也在逐年增加。最近的研究表明，在抑郁症发病期间，大脑中长链非编码RNA（lncRNA）表达的改变会影响神经发育，并对抑郁症具有调节功能。但是大多数lncRNA的功能尚未被研究。在本研究中，我们利用慢性不可预知温和应激（CUMS）抑郁小鼠模型，用抗抑郁药氟西汀进行6周干预后，分析了在抑郁样行为小鼠模型以及氟西汀干预后的CUMS小鼠海马组织中lncRNA的表达水平的差异。结果发现，与正常小鼠相比，CUMS诱导的小鼠海马组织中共有282个lncRNA差异表达，其中134个lncRNA在CUMS抑郁样小鼠中表达上调，148个lncRNA在CUMS抑郁样小鼠中表达下调）（P<0.05）。在氟西汀干预后，与CUMS抑郁样小鼠相比，我们发现370个lncRNA呈现差异表达。我们进一步对这些差异表达的lncRNA进行GO功能分析发现，差异表达的lncRNA与蛋白结合，氧结合和转运活性之间存在关联。通过基因和基因组百科全书（KEGG）信号通路分析表明，失调的lncRNA可能参与了炎症反应途径。氟西汀可通过调节海马中lncRNA的表达来有效缓解CUMS诱导的小鼠抑郁症状。本文的发现为老年抑郁症发生的潜在机制提供了有价值的见解。.
Keywords: Chronic unpredictable mild stress; Depression; Elderly; Fluoxetine; LncRNA.