Social Interaction in Neuroprotection and Lifespan of Drosophila SOD Mutants

描述（由申请人提供）：我们发现在铜/锌超氧化物歧化酶（Sod）缺陷的果蝇Sod突变体中，社会互动具有显著的、强大的延长寿命效应。缺乏SOD酶活性会阻碍动物清除有氧代谢过程中产生的有害活性氧（ROS）的能力，导致衰老加速和过度应激反应，并与几种神经退行性疾病有关。我们发现，在与更年轻或更活跃的果蝇共同居住时，Sod突变体不仅表现出两倍的寿命，而且还表现出更好的抗逆性和运动协调性。这些表型为干预和揭示某些神经保护机制和寿命决定背后的相互作用的遗传网络和代谢途径提供了一个敏感的系统。我们将采用多学科的方法，利用我们实验室和合作者开发的分子、遗传、生理和行为工具来促进相关性

DESCRIPTION (provided by applicant): We found a striking, robust life-span extension effect of social interaction in Drosophila Sod mutants defective in Cu/Zn superoxide dismutase (SOD). Lacking SOD enzymatic activity hampers the ability of animals to clear the harmful reactive oxygen species (ROS) generated in aerobic metabolic process, leading to accelerated aging and excessive stress responses, and is implicated in several neurodegenerative diseases. We found that upon co-housing with younger or more active flies, Sod mutants display not only a doubled lifespan, but also improved stress-resistance and motor coordination. These phenotypes provide a sensitized system for intervention and for unraveling the interacting genetic networks and metabolic pathways underlying certain neuroprotective mechanisms and lifespan determination. We will adopt a multi-disciplinary approach with the molecular, genetic, physiological and behavioral tools developed in our lab and collaborators to facilitate correlation within the same individual or groups of flies subjected to studies at different levels. Aim1: To refine the behavioral experiments to reveal the nature of beneficial behavioral interactions for further understanding of the neuroprotective effect of social interaction in Sod flies. We aim to use the automated video tracking system, IowaFLI Tracker, newly developed in our lab in conjunction with other standard behavioral techniques. Aim2: Sod flies with or without co-housed helpers will be examined for key redox enzymes or their substrates by qRT-PCR and Western Blot analysis to uncover their potential roles in the helper effect, as suggested by their compensatory adjustments in ROS metabolism in this neuroprotective process. In addition a large extant collection of double mutants among genes controlling membrane excitability and metabolic pathways will facilitate construction of an interaction map linking metabolic pathways and neuronal excitability control emanating from Sod function. Missing links and new branches from prominent responder genes may emerge through a microarray analysis. Aim3: The beneficial effects of improved motor coordination and stress resistance will be further correlated with physiological modifications in neurons and neural circuits during aging of Sod flies co-housed with helpers. We will identify resilient physiological parameters as well as labile properties that are prone to Sod mutational perturbations. This will define in concrete physiological terms the landmarks of nervous system aging that are responsive to neuroprotective effect of social interactions.