ALBERT

Description: A comprehensive understanding of the effects of spaceflight and altered gravity on human physiology is necessary for continued human space exploration and long-term space habitation. The oxidative stress response has been identified in astronauts exposed to short- and long-term space missions that are exposed to the multitude of stress factors of spaceflight, including altered gravity and radiation exposure. Reactive oxygen species (ROS) are byproducts of homeostatic cellular metabolism, yet when overproduced the oxidative stress response ensues, rendering molecules destructive causing cell death and inflammation. Controlling aberrant ROS production is necessary to prevent pathological consequences, in particular within the nervous system, since neurons are extremely sensitive overexpressed ROS insults. We hypothesize that exposure to altered gravity triggers the oxidative stress response, leading to impairments in the nervous system. In this study, we used a well-established spaceflight model organism, Drosophila melanogaster, to assess altered gravity associated changes in the nervous system using a ground-based hypergravity model. Acute hypergravity resulted in an induction of oxidative stress-related genes with an increase in reactive oxygen species (ROS) in fly brains (p〈0.001). Also, qPCR analysis shows that parkin gene expression is significantly reduced in these fly brains(p〈0.05). Additionally, chronic hypergravity resulted in depressed locomotor phenotype in these flies (p〈0.05) in conjunction to decreased dopaminergic neuron counts (p〈0.0001) and increased apoptosis in these fly brains (p〈0.0001). Further, assessment of neurological changes, including the neuronal architecture, synaptic integrity and genetic regulation caused by hypergravity conditions were noted. Overall, our results validate chronic hypergravity simulation as a behavioral model to study spaceflight effects, and oxidative stress pathway as a potential avenue for countermeasure development for astronauts undergoing short- and long-term missions and for neurodegenerative research on Earth.