The effect of aging on sensory neurons in C. elegans using in vivo imaging

描述（由申请人提供）：从生物学角度来看，衰老是一种退行性过程，通常与年龄相关疾病或残疾的高概率、身体和精神功能能力低下以及对生活的参与度低相关。 揭示整体神经元功能以及特定神经元特性如何随年龄变化被认为是理解年龄相关疾病和障碍的分子机制的重要一步。 衰老的多变量、环境依赖性导致采用易于遗传操纵、寿命短并且可以在可控的实验室环境中发育和衰老的动物模型。 在过去的30年里，C。线虫是一种微小的线虫，具有强大的遗传学和明确的神经系统，已成为研究衰老过程的重要模式生物。 我们建议将联合收割机钙成像与微流控技术相结合，以量化衰老对C. elegans in vivo. 我们假设秀丽隐杆线虫感觉神经元的生物物理特性随着年龄的增长而改变。 我们还假设氧化应激是导致神经元性能下降的一个因素，抗氧化应激物质可以最大限度地减少氧化损伤。 通过使用钙指示剂，我们将能够探测这些神经元在被某种刺激触发时的生物物理特性（神经元敏感性、时间响应和去极化幅度）。 微流体技术将提供从大量蠕虫中获得可重复和准确成像数据所需的自动化。 为了验证我们的假设，将比较不同年龄的各种蠕虫（野生型，突变体和抗氧化剂处理的蠕虫）的成像数据，并获得统计学显著的趋势。 公共卫生相关性：衰老与年龄相关疾病（帕金森病和阿尔茨海默病）的高概率，身体和精神功能能力低下以及对生活的参与度低有关。 我们拟研究衰老对线虫感觉神经元的影响。elegans使用在体内钙成像和微流体技术。 我们相信，我们的研究将加深我们对更复杂神经系统衰老过程的理解

DESCRIPTION (provided by applicant): Aging, a degenerative process when viewed from the biological prospective, is often associated with a high probability of an age-related disease or disability, low physical and mental function capacity and low engagement with life. Revealing how the overall neuronal functionality and how specific neuronal properties alter with age is considered to be a major step towards understanding the molecular mechanisms of age-related diseases and disorders. The multivariate, environment-dependant character of aging, led to the adoption of animal models that can be easily genetically manipulated, have a short lifespan and can develop and age in a controllable lab environment. Over the last three decades, C. elegans, a tiny nematode with powerful genetics and a well-defined nervous system, has become a prominent model organism for studying the process of aging. We propose to combine calcium imaging with microfluidics to quantify the effect of aging to the functionality of major sensory neurons (ASH, AWC, AFD) of C. elegans in vivo. We hypothesize that the biophysical properties of the sensory neurons in C.elegans are altered with age. We also hypothesize that oxidative stress is one factor that results in the degradation in the neuronal performance and that anti-oxidative stress substances can minimize oxidative damage. By using calcium indicators, we will be able to probe the biophysical properties (neuronal sensitivity, time response and amplitude of depolarization) of these neurons when triggered with a certain stimulus. The microfluidics will provide the automation that is required for obtaining repeatable and accurate imaging data from a large number of worms. In order to validate our hypotheses, imaging data from various populations of worms (wild-type, mutants and antioxidants-treated worms) of different ages will be compared and statistically significant trends will be obtained. PUBLIC HEALTH RELEVANCE: Aging is associated with a high probability of age-related diseases (Parkinson's and Alzheimer's disease), low physical and mental functional capacity and low engagement with life. We propose to study the effect of aging on sensory neurons in the nematode C. elegans using in vivo calcium imaging and microfluidic technology. We believe that our studies will deepen our understanding of the aging process in more sophisticated nervous systems