Astronauts on interplanetary missions-such as to Mars-will be exposed to space radiation, a spectrum of highly-charged, fast-moving particles that includes 56 fe and 28 Si. earth-based preclinical studies show space radiation decreases rodent performance in low-and some high-level cognitive tasks. Given astronaut use of touchscreen platforms during training and space flight and given the ability of rodent touchscreen tasks to assess functional integrity of brain circuits and multiple cognitive domains in a non-aversive way, here we exposed 6-month-old C57BL/6J male mice to whole-body space radiation and subsequently assessed them on a touchscreen battery. Relative to Sham treatment, 56 fe irradiation did not overtly change performance on tasks of visual discrimination, reversal learning, rule-based, or object-spatial paired associates learning, suggesting preserved functional integrity of supporting brain circuits. Surprisingly, 56 fe irradiation improved performance on a dentate gyrus-reliant pattern separation task; irradiated mice learned faster and were more accurate than controls. Improved pattern separation performance did not appear to be touchscreen-, radiation particle-, or neurogenesisdependent, as 56 fe and 28 Si irradiation led to faster context discrimination in a non-touchscreen task and 56 fe decreased new dentate gyrus neurons relative to Sham. these data urge revisitation of the broadly-held view that space radiation is detrimental to cognition. Interplanetary missions-such as to Mars-are a high priority for many space agencies. The crew of future missions will face hazards 1-3 , such as exposure to galactic cosmic radiation 4-7 a spectrum of low and high-(H) atomic number (Z) and high-energy (E) particles such as 56 Fe and 28 Si. Fast-moving HZE particles cannot be effectively blocked by modern spacecraft shielding 8-11. Therefore, it is concerning that studies with laboratory animals generally conclude HZE particles are detrimental to brain and behavior 12-14. Such preclinical data suggest HZE particle exposure may be harmful to astronaut cognition and impede mission success.

High-charge and -energy (HZE) particles comprise space radiation and they pose a challenge to astronauts on deep space missions. While exposure to most HZE particles decreases neurogenesis in the hippocampus—a brain structure important in memory—prior work suggests that 12C does not. However, much about 12C’s influence on neurogenesis remains unknown, including the time course of its impact on neurogenesis. To address this knowledge gap, male mice (9–11 weeks of age) were exposed to whole-body 12C irradiation 100 cGy (IRR; 1000 MeV/n; 8 kEV/µm) or Sham treatment. To birthdate dividing cells, mice received BrdU i.p. 22 h post-irradiation and brains were harvested 2 h (Short-Term) or three months (Long-Term) later for stereological analysis indices of dentate gyrus neurogenesis. For the Short-Term time point, IRR mice had fewer Ki67, BrdU, and doublecortin (DCX) immunoreactive (+) cells versus Sham mice, indicating decreased proliferation (Ki67, BrdU) and immature neurons (DCX). For the Long-Term time point, IRR and Sham mice had similar Ki67+ and DCX+ cell numbers, suggesting restoration of proliferation and immature neurons 3 months post-12C irradiation. IRR mice had fewer surviving BrdU+ cells versus Sham mice, suggesting decreased cell survival, but there was no difference in BrdU+ cell survival rate when compared within treatment and across time point. These data underscore the ability of neurogenesis in the mouse brain to recover from the detrimental effect of 12C exposure.

No abstract

Astronauts on interplanetary space missions -such as to Mars -will be exposed to space radiation, a spectrum of highly-charged, fast-moving particles that includes 56 Fe and 28 Si. Earth-based preclinical studies with mature, "astronaut-aged" rodents show space radiation decreases performance in lowand some high-level cognitive tasks. Given the prevalence of touchscreens in astronaut training and in-mission assessment, and the ability of rodent touchscreen tasks to assess the functional integrity of brain circuits and multiple cognitive domains in a non-aversive way, it is surprising the effect of space radiation on rodent touchscreen performance is unknown. To fill this knowledge gap, 6-month-old C57BL/6J male mice were exposed to whole-body space radiation and assessed on a touchscreen battery starting 1-month later. Relative to Sham, 56 Fe irradiation did not overtly change performance on tasks of visual discrimination, reversal learning, rule-based, or object-spatial paired associates learning, suggesting preserved functional integrity of supporting brain circuits.Surprisingly, 56 Fe irradiation led to better performance on a dentate gyrus-reliant task of pattern separation ability. Irradiated mice discriminated similar visual cues in ~40% fewer days and ~40% more accurately than control mice. Improved pattern separation was not touchscreen-, radiation-particle, or neurogenesis-dependent, as both 56 Fe and 28 Si irradiation led to faster context discrimination (e.g. Sham Block 5 vs. 56 Fe Block 2) in a non-touchscreen task and 56 Fe led to fewer new dentate gyrus neurons relative to Sham. These data urge revisitation of the broadly-held view that space radiation is detrimental to cognition. SIGNIFICANCE STATEMENTAstronauts on an interplanetary mission -such as to Mars -will be unavoidably exposed to galactic cosmic radiation, a spectrum of highly-charged, fast-moving particles. Rodent studies suggest space radiation is detrimental to cognition. However, here we show this is not universally true. Mature mice that received whole body exposure to Mars-relevant space radiation perform similarly to control mice on high-level cognitive tasks, reflecting the functional integrity of key neural circuits. Even more surprisingly, irradiated mice perform better than controls in both appetitive and aversive tests of pattern separation, a mission-critical task reliant on dentate gyrus integrity. Notably, improved pattern separation was not touchscreen-, radiation-particle-, or neurogenesis-dependent. Our work urges revisitation of the generally-accepted conclusion that space radiation is detrimental to cognition.3 RESULTS Mice exposed to whole body 56 Fe radiation demonstrate overall normal perceptual discrimination, association learning, and cognitive flexibility in touchscreen testing.Whole body 56 Fe IRR was delivered via fractionation (Frac; 3 exposures of 6.7 cGy every other day, total 20 cGy) to male C57BL/6J mice at 6 mon of age. This total dose is submaximal to that predicted for a Mars mission (9, 66) , and the fr...

Cardiovascular disease (CVD) remains the leading cause of death in American women. Despite advancements in the management of CVD, the death rates have plateaued over the past decade, particularly in females under the age of 65. 1,2 One third of new-onset cardiovascular events in women occur before the age of 65, which emphasize the need for improved screening strategies in younger women to target preventative therapies. 3 When assessing women for primary prevention of CVD, several risk scores exist with the most recent being the atherosclerotic cardiovascular disease (ASCVD) risk score, also known as the pooled