Spaceflight affects neuronal morphology and alters transcellular degradation of neuronal debris in adult Caenorhabditis elegans

This is the final version. Available on open access from Cell Press via the DOI in this record.Data and code availability: No large-scale data sets or codes were generated or analyzed in this study. We deposited detailed temperature recordings from spaceflight and control samples in Harvard Dataverse: https://doi.org/10.7910/DVN/ATOJCJ. The raw data supporting the current study are available from the lead contact upon request.Abstract: Extended space travel, such as crewed missions to Mars and beyond, is a goal for both government space agencies and private companies. Research over the past decades, however, has shown that spaceflight poses risks to human health, including negative effects on musculoskeletal, cardiovascular, and immune systems. Details regarding effects on the nervous system have been less well described. The use of animal models holds great potential to identify and dissect conserved mechanisms of neuronal response to spaceflight. Here, we exploited the unique experimental advantages of the nematode Caenorhabditis elegans to explore how spaceflight affects adult neurons in vivo, at the single-cell level. We found that animals that lived 5 days of their adult life on the International Space Station exhibited considerable dendritic remodeling of the highly branched PVD neuron and modest morphological changes in touch receptor neurons when compared to ground control animals. Our results indicate hyperbranching as a common response of adult neurons to spaceflight. We also found that, in the presence of a neuronal proteotoxic stress, spaceflight promotes a remarkable accumulation of neuronal-derived waste in the surrounding tissues (especially hypodermis), suggesting an impaired transcellular degradation of debris that is released from neurons. Overall, our data reveal that spaceflight can significantly affect adult neuronal morphology and clearance of neuronal trash, highlighting the need to carefully assess the risks of long-duration spaceflight on the nervous system and to develop countermeasures to protect human health during space exploration.European Space AgencyNational Aeronautics and Space Administration (NASA