Music compensates for altered gene expression in age-related cognitive disorders

Extensive literature has explored the beneficial effects of music in age-related cognitive disorders (ACD), but limited knowledge exists regarding its impact on gene expression. We analyzed transcriptomes of ACD patients and healthy controls, pre-post a music session (n=60), and main genes/pathways were compared to those dysregulated in mild cognitive impairment (MCI) and Alzheimer’s disease (AD) as revealed by a multi-cohort study (n=1269 MCI/AD and controls). Music was associated with 2.3 times more whole-genome gene expression, particularly on neurodegeneration-related genes, in ACD than controls. Co-expressed gene-modules and pathways analysis demonstrated that music impacted autophagy, vesicle and endosome organization, biological processes commonly dysregulated in MCI/AD. Notably, the data indicated a strong negative correlation between musically-modified genes/pathways in ACD and those dysregulated in MCI/AD. These findings highlight the compensatory effect of music on genes/biological processes affected in MCI/AD, providing insights into the molecular mechanisms underlying the benefits of music on these disorders. Music exerts a profound influence on human brains, affecting emotions, activating the reward system, and inducing changes in brain anatomy. However, research on the impact of music on gene expression is still in its nascent stages. The present study represents the first attempt to analyze the effect of music on the transcriptome of ACD patients. Capillary blood samples were collected from ACD patients and healthy donors using a minimally invasive procedure before and after a 50-minute session of classical musical stimuli in an ecologically valid environment. Subsequently, we performed RNA sequencing on these samples, allowing for the analysis of gene expression information for over 35,000 transcripts. The analysis focused on differential expression between the two time points and cohorts, as well as the contextualization of gene expression changes within the framework of genes and pathways that exhibit dysregulated expression in MCI and AD

已有大量文献探讨了音乐对年龄相关性认知障碍（age-related cognitive disorders, ACD）的有益作用，但关于其对基因表达的影响，目前认知仍十分有限。本研究分析了60名年龄相关性认知障碍患者与健康对照在音乐干预前后的转录组，并结合一项纳入1269名轻度认知障碍（mild cognitive impairment, MCI）、阿尔茨海默病（Alzheimer’s disease, AD）患者及健康对照的多队列研究数据，对比了核心基因与通路的失调情况。与健康对照相比，年龄相关性认知障碍患者经音乐干预后，全基因组基因表达变化幅度提升2.3倍，尤以神经退行性相关基因为著。共表达基因模块与通路分析表明，音乐可调控自噬、囊泡与内体组织等在MCI/AD中普遍失调的生物学过程。值得注意的是，数据显示，年龄相关性认知障碍患者中经音乐调控的基因/通路，与MCI/AD中失调的基因/通路呈显著负相关。上述结果揭示了音乐对MCI/AD受累基因及生物学过程的代偿作用，为阐明音乐改善此类疾病的分子机制提供了新视角。音乐对人脑具有深远影响，可调节情绪、激活奖赏系统并引发脑解剖结构改变，但目前关于音乐对基因表达影响的研究仍处于起步阶段。本研究首次尝试探讨音乐对年龄相关性认知障碍患者转录组的调控作用。研究在生态效度良好的环境中，为60名年龄相关性认知障碍患者与健康对照实施了50分钟的古典音乐刺激，并于干预前后采用微创方式采集毛细血管血样。随后对上述样本进行RNA测序，得以分析超过35000个转录本的基因表达信息。本次分析重点关注两个时间点及不同队列间的差异表达情况，并将基因表达变化锚定至MCI与AD中存在表达失调的基因及通路框架内。