Impact of the ISS Environment on CNS in Drosophila Melanogaster

Altered gravity and elevated carbon dioxide (CO2) levels as experienced on the ISS can adversely affect human health across various organ systems, especially the Central Nervous System (CNS). Investigating these changes is essential for understanding the long-term effects of spaceflight on human physiology to ensure crew health. Ground-based analogs provide an efficient method to evaluate alterations induced by chronic spaceflight on a larger scale. This study focuses on CNS changes in response to hypergravity (HG) and elevated CO2 levels via a ground-based analog using the well-established model organism, Drosophila melanogaster. We hypothesize behavior and physiological changes immediately post exposure to HG+CO2, along with chronic effects up to 25 days post-exposure. Adult male and female flies were exposed to varying gravity loads (1g, 1.2g, and 3g) and elevated CO2 levels (~4000 ppm, mimicking CO2 levels on the ISS) for 15 days and were assessed immediately and at 5-, 10-, and 25-days post-exposure, mirroring astronauts’ post-return profiling. The flies were assessed for neurobehavioral changes, including longevity and negative geotaxis; brain morphological changes, such as dopaminergic neuron count, apoptosis, and glial cell density; and bioenergetic changes in the brain, including mitochondrial abundance and membrane potential. Longevity remained unchanged under hypergravity, even with the addition of elevated CO2 as a stressor. However, despite the stable lifespan, quality of life appeared to be affected, as shown by negative geotaxis and neuroanatomical changes. Negative geotaxis testing revealed a reduction in motor ability at R0 across all conditions, which correlated with a decrease in dopaminergic (DA) neuron count. Additional observations suggested further systemic alterations, including a decrease in glial cell count, an increase in apoptosis, and notable bioenergetic changes. Collectively, these findings contribute to our understanding of the long-term effects of spaceflight on the CNS.