Nonhuman primate models in the study of spaceflight stressors: Past contributions and future directions

Studies in rodents suggest that exposure to distinct spaceflight stressors (e.g., space radiation, isolation/confinement, microgravity) may have a profound impact on an astronaut's ability to perform both simple and complex tasks related to neurocognitive performance, central nervous system (CNS) and vestibular/sensorimotor function. However, limited information is currently available on how combined exposure to the spaceflight stressors will impact CNS-related neurocognitive and neurobiological function in-flight and, as well, terrestrial risk of manifesting neurodegenerative conditions when astronauts return to earth. This information gap has significantly hindered our ability to realistically estimate spaceflight hazard risk to the CNS associated with deep space exploration. Notwithstanding a significant body of work with rodents, there have been very few direct investigations of the impact of these spaceflight stressors in combination and, to our knowledge, no such investigations using nonhuman primate (NHP) animal models. In view of the widely-recognized translational value of NHP data in advancing biomedical discoveries, this research deficiency limits our understanding regarding the impact of individual and combined spaceflight stressors on CNS-related neurobiological function. In this review, we address this knowledge gap by conducting a systematic and comprehensive evaluation of existing research on the impact of exposure to spaceflight stressors on NHP CNS-related function. This review is structured to: a) provide an overarching view of the past contributions of NHPs to spaceflight research as well as the strengths, limitations, and translational value of NHP research in its own right and within the existing context of NASA-relevant rodent research; b) highlight specific conclusions based on the published literature and areas needed for future endeavors; c) describe critical research gaps and priorities in NHP research to facilitate NASA's efforts to bridge the key knowledge gaps that currently exist in translating rodent data to humans; and d) provide a roadmap of recommendations for NASA regarding the availability, validity, strengths, and limitations of various NHP models for future targeted research.