微流控方法关联神经元功能衰老与机械感知相关基因表达的变化
Microfluidic approach to correlate neuronal functional aging and underlying changes of gene expression in mechanosensation.
机构信息
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, USA.
Petit Institute for Bioengineering and Bioscience, Interdisciplinary BioEngineering Program, Georgia Institute of Technology, Atlanta, GA 30332, USA.
出版信息
Lab Chip. 2024 May 14;24(10):2811-2824. doi: 10.1039/d3lc01080e.
The aging process has broad physiological impacts, including a significant decline in sensory function, which threatens both physical health and quality of life. One ideal model to study aging, neuronal function, and gene expression is the nematode , which has a short lifespan and relatively simple, thoroughly mapped nervous system and genome. Previous works have identified that mechanosensory neuronal structure changes with age, but importantly, the actual age-related changes in the function and health of neurons, as well as the underlying genetic mechanisms responsible for these declines, are not fully understood. While advanced techniques such as single-cell RNA-sequencing have been developed to quantify gene expression, it is difficult to relate this information to functional changes in aging due to a lack of tools available. To address these limitations, we present a platform capable of measuring both physiological function and its associated gene expression throughout the aging process in individuals. Using our pipeline, we investigate the age-related changes in function of the mechanosensing ALM neuron in , as well as some relevant gene expression patterns ( and ). Using a series of devices for animals of different ages, we examined subtle changes in neuronal function and found that while the magnitude of neuronal response to a large stimulus declines with age, sensory capability does not significantly decline with age; further, gene expression is well maintained throughout aging. Additionally, we examine PVD, a harsh-touch mechanosensory neuron, and find that it exhibits a similar age-related decline in magnitude of neuronal response. Together, our data demonstrate that our strategy is useful for identifying genetic factors involved in the decline in neuronal health. We envision that this framework could be applied to other systems as a useful tool for discovering new biology.
衰老过程具有广泛的生理影响,包括感觉功能的显著下降,这威胁到身体健康和生活质量。研究衰老、神经元功能和基因表达的理想模型是线虫,它的寿命短,神经系统和基因组相对简单,并且已经被彻底绘制出来。以前的研究已经确定了机械感觉神经元的结构随年龄而变化,但重要的是,神经元的功能和健康以及导致这些衰退的潜在遗传机制的实际年龄相关变化尚未完全了解。虽然已经开发出单细胞 RNA 测序等先进技术来定量基因表达,但由于缺乏可用的工具,很难将这些信息与衰老过程中的功能变化联系起来。为了解决这些限制,我们提出了一个能够在个体的整个衰老过程中测量生理功能及其相关基因表达的平台。使用我们的流水线,我们研究了机械感觉 ALM 神经元在衰老过程中的功能相关变化,以及一些相关的基因表达模式(和)。我们使用一系列针对不同年龄动物的设备,检查了神经元功能的细微变化,发现虽然神经元对大刺激的反应幅度随年龄的增长而下降,但感觉能力并没有随年龄的增长而显著下降;此外,基因表达在整个衰老过程中得到很好的维持。此外,我们还研究了 PVD,一种强烈触觉机械感觉神经元,发现它也表现出与神经元反应幅度相关的相似的年龄相关下降。总之,我们的数据表明,我们的策略对于鉴定与神经元健康下降相关的遗传因素是有用的。我们设想,该框架可以作为一种发现新生物学的有用工具,应用于其他系统。