Neurobiological and neurophysiological impacts of real spaceflight and simulated microgravity on C. elegans: a...

The modern phase of human exploration highlights the critical need to understand and mitigate the effects of spaceflight on the human body. Since the first lunar missions, prolonged exposure to microgravity and space radiation has been associated with challenges to the musculoskeletal, immune, and cardiovascular systems; however, the nervous system is emerging as a particularly sensitive target. This review highlights Caenorhabditis elegans (C. elegans) as a model for examining spaceflight-induced neuronal changes, due to its conserved molecular pathways and well-understood nervous system. Recent research shows that microgravity causes morphological changes, including dendritic hyperbranching and self-avoidance defects, which disturb receptive field structure and impair sensory integration. Simultaneously, neuronal waste clearance via exopher pathways becomes less effective, leading to proteostatic overload and feedback stress affecting neuronal function. At a neurochemical level, dopamine and acetylcholine signalling are notably disrupted, while serotonergic and GABA systems also show vulnerabilities, collectively impacting locomotion, behavioral flexibility, and stress resilience. By integrating behavioral, pathological, and molecular insights, this review links neuronal branching, waste clearance, and neurotransmitter regulation as a unified axis of functional disturbance. Ongoing research using C. elegans is crucial to uncover mechanistic pathways and develop countermeasures to safeguard astronaut neurological health, resilience, and performance during future long-duration missions.