Abstract
Long-duration crewed exploration missions beyond low Earth orbit will expose astronauts to chronic, low-dose-rate galactic cosmic rays (GCRs), posing substantial risks to central nervous system integrity and operational performance. In this study, we investigated the persistent neurocognitive consequences of simulated GCR exposure in adult C57BL/6J mice using a broad-spectrum, high-energy particle accelerator beamline. Cohorts of male and female mice were subjected to either sham irradiation or a simplified 6-ion GCR simulation spectrum delivering cumulative absorbed doses of 15 cGy, 30 cGy, or 50 cGy. Behavioral and cognitive profiling conducted at 90 and 180 days post-exposure revealed marked, dose-dependent deficits in cognitive flexibility and spatial working memory, as assessed by the Barnes maze and novel object recognition paradigms. Immunohistochemical and morphological analyses of the prefrontal cortex and hippocampus demonstrated persistent microglial activation (elevated Iba1 expression and soma swelling) alongside significant reductions in dendritic branching and spine density in CA1 pyramidal neurons. Interestingly, female cohorts exhibited attenuated neuroinflammatory signatures and partial preservation of recognition memory compared to males at equivalent dose thresholds. These findings confirm that biologically relevant doses of high-charge and energy (HZE) particle radiation induce long-lasting structural remodeling and neuroinflammation in brain circuits critical for executive function, underscoring the urgent need for validated neuroprotective countermeasures prior to interplanetary transit.
