MICROGRAVITY-INDUCED ALTERATIONS IN THE BRAIN-TO-BONE AXIS: IMPLICATIONS FOR BONE LOSS AND COUNTERMEASURE DEVELOPMENT IN LONG-TERM SPACEFLIGHT.

Space exploration over the next 30 to 50 years is projected to initially return to the Moon, with the creation of a permanent lunar settlement, followed by the establishment of a human colony on Mars. To ensure the success of these missions beyond low Earth orbit, it is essential to thoroughly investigate the effects of space environments on human physiology, crew performance, and overall health. While anti-resorptive drugs, a proper diet, and vitamin and mineral supplementation are used to address the issue today, this approach is insufficient for more than six months in microgravity. Thus, it is paramount for the first astronauts landing on Mars to be able to explore the Red Planet's surface upon arrival. This limitation is critical, as astronauts landing on Mars must be capable of immediate surface exploration and functioning upon arrival. Even with these countermeasures and intensive postflight reconditioning, full recovery is a lengthy process that often leaves scars, despite some studies indicating that it remains incomplete. Muscle atrophy and loss of strength may result from neurophysiological deterioration affecting both bone and muscle, including impaired synaptic transmission. Previous studies have already shown that microgravity has a detrimental effect on motor neuron function. Within this scope, this research aims to deepen the understanding of brain-bone interaction in space by exposing rodents to simulated microgravity for 16 hours daily over four weeks using a Random Positioning Machine (RPM). In this study, we successfully identified bone denervation in microgravity while simultaneously producing an imbalance in neurotransmitter signaling, providing novel empirical evidence on the effects of microgravity on the brain-bone axis.