Studying Parkinson's Disease-Like Molecular Changes in Dopaminergic Neurons Exposed to Simulated Microgravity

Space flight (SF) exposes astronauts to various stressors, including microgravity, cosmic radiation, hypercapnia, ischemia, isolation, and confinement, the long-term effects of which have been linked to the onset of neurodegenerative disorders such as Parkinson’s disease (PD). This ground-based study investigates the effects of one such SF stressor—simulated microgravity (SMG)—on dopaminergic neurons, specifically focusing on its potential to induce PD-related neurodegeneration. We used a custom-built clinostat to simulate microgravity in neuronal cultures and characterized its operation by measuring the G-forces experienced by the neurons using an accelerometer. To evaluate the effects of SMG on cellular stress and degeneration, we conducted mitochondrial health analysis, image analysis, and neuronal morphometric assessments on neurons exposed to SMG. Furthermore, we employed qPCR and Western blot techniques to examine the time-dependent impact of SMG on PD-like molecular signatures in these neurons, including alterations in key PD-related markers. Our findings suggest that exposure to SMG induces molecular and morphological changes consistent with PD-like pathology in dopaminergic neurons. Given the planned manned missions to the Moon and Mars, understanding the impact of prolonged simulated microgravity (SMG) on neurodegenerative diseases is crucial. Continued research is essential to identify the risks of such neurodegeneration and to develop effective countermeasures that can mitigate these effects during long-duration space travel.