Impact of spaceflight stressors on behavior and cognition: A molecular, neurochemical, and neurobiological perspective.

The response of the human body to multiple spaceflight stressors is complex, but mounting evidence implicate risks to CNS functionality as significant, able to threaten metrics of mission success and longer-term behavioral and neurocognitive health. Prolonged exposure to microgravity, sleep disruption, social isolation, fluid shifts, and ionizing radiation have been shown to disrupt mechanisms of homeostasis and neurobiological well-being. The overarching goal of this review is to document the existing evidence of how the major spaceflight stressors, including radiation, microgravity, isolation/confinement, and sleep deprivation, alone or in combination alter molecular, neurochemical, neurobiological, and plasma metabolite/lipid signatures that may be linked to operationally-relevant behavioral and cognitive performance. While certain brain region-specific and/or systemic alterations titrated in part with neurobiological outcome, variations across model systems, study design, and the conspicuous absence of targeted studies implementing combinations of spaceflight stressors, confounded the identification of specific signatures having direct relevance to human activities in space. Summaries are provided for formulating new research directives and more predictive readouts of portending change in neurobiological function.

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.