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On a wet Wednesday in June, 1783, the first hot air balloon lifted into the sky in the French city of Annonay. It travelled three thousand feet into the air and was carried aloft for nearly two miles, eventually touching down in a vineyard. It flew empty; safety wasn’t a guarantee. A couple of months later, another balloon was sent floating above Paris, this time ferrying a sheep, a duck, and a rooster. The duck was expected to be okay, given its proclivity for flying, but onlookers weren’t so sure about the sheep and rooster, earthbound creatures as they are, like us. After travelling a similar height and distance as the first balloon, the animals were found to be unharmed after landing (although the sheep had peed everywhere). The inaugural balloon ride by a human soon followed, and with it the age of aviation began in earnest.

Today, the thought of sending people skyward seems banal, unless the final destination is another planet like Mars or, eventually, Proxima b. Those far-off destinations bring a new set of concerns about the health of human explorers—it’s no longer merely a question of whether our rockets and spacesuits will fail. Instead, researchers are working to uncover the intricate, insidious changes expected to occur in the human body during prolonged deep space voyages, in part the results of weightlessness (microgravity) and ionizing radiation. In space, says Ruthan Lewis, an architect and engineer at NASA’s Goddard Flight Center, “You’re constantly being bombarded.”

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It turns out that disrupting the state in which our bodies evolved, under the constraints of Earth’s gravity, while being zapped by high-energy atoms and photons, isn’t particularly good for our brains. Scientists have shown that these deep space hazards inhibit mental processes, such as reasoning and memory, but it wasn’t really clear why. Two recent studies, though, using mice and rats, have helped researchers understand how this happens.

In the first study, conducted by a team of five researchers from Loma Linda University, mice had their hindquarters hoisted off the ground for long periods of time, to mimic microgravity, and were situated next to a plate of radioactive cobalt, to mimic low level but long-term exposure to gamma radiation. The researchers found evidence that the combination of both damaged the blood-brain barrier—a collection of tightly joined cells that prevent most substances in the bloodstream from reaching the brain—to a greater extent than exposure to either factor on its own.

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They could tell by the relatively elevated presence in the brain of a water-regulating protein called aquaporin-4, known to increase in quantity when the blood-brain barrier is compromised. This was determined by killing the mice, staining several sections of their brains using an aquaporin-4-binding antibody, followed by a second antibody with a high affinity for the first antibody, bearing a green-fluorescing dye, and then measuring the intensity of the fluorescence by each brain section, as an indicator of the amount of protein present. The increase in aquaporin-4 was associated with subtle behavioral changes in the mice, including increased risk-taking, assessed based on how much time a mouse spent exposed (and so more vulnerable to predators) in an elevated zero maze, a circular loop consisting of alternating open and enclosed sections.

Microgravity- and radiation-exposed mice were willing to hang out in the open sections for a greater percentage of time compared to unexposed mice. It’s not exactly clear why an increase in aquaporin-4 results in more risk-taking, but it may be related to inflammation-driven damage caused by white blood cells, and their products in the blood outside of the brain, traversing the blood-brain barrier. This suggests Mars-bound astronauts will be less risk-averse travelling through deep space than normal, which could—given the unforgiving nature of outer space—influence the success of their mission. Ensuring risks are effectively managed becomes more difficult if the risk-taking behavior of a crew changes over the course of a journey.

The second study, by Andrew J. Wyrobek, a biophysicist at the University of California, Berkeley, and Richard A. Britten, a radiobiologist at Eastern Virginia Medical School, showed that bombarding rats with high-speed iron atoms (a form of particle radiation, as opposed to the gamma radiation featured in the first study) disrupted their spatial memory learning. Over three days, after having exposed them to one of five incremental doses of radiation, the researchers tested the rats’ ability to escape a Barnes maze, essentially a circular dinner table with 20 holes—only one being the true exit—evenly spaced around the surface’s perimeter. “The average unirradiated rat took about half as much time to find the escape hole on day 3 (the last day of training) compared to the first day of training,” the researchers write, but animals who received a dose of 20 grays, in line with the expected radiation exposure while on a long space trip, on average, actually “took more time to find the location of the escape hole on the last versus first day of training” (emphasis mine).

This is concerning, given that spatial memory learning is a fundamental part of the many tasks deep space voyagers will no doubt have to execute, be it piloting the spacecraft or carrying out maintenance and repairs on ship infrastructure.

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However, there appears to be a genetic component to how susceptible the rats’ learning abilities were to radiation. Even though they were distantly related, rats receiving the same doses of radiation weren’t affected equally with respect to their spatial learning and memory. A closer inspection of the data revealed there were two groups of rats, poor learners and good learners. The observed average decline in spatial memory learning with an increasing radiation dose was driven by the poor learners in each exposure group, with the good learners not exhibiting any appreciable change in their learning behavior due to radiation exposure.

The same genetic variability might exist in people, influencing our approach to the next leg of space exploration. As the authors muse in their discussion, “In the future, we might become able to prescreen space travelers or cancer patients to distinguish between individuals who are resistant versus susceptible to radiation-induced neurotoxicity and abnormal behavior responses.”

It’s likely we’ll also need to employ onboard countermeasures such as radiation shielding—perhaps strategically placed water, plastic, or some newly fabricated material or force field, says Sheila Thibeault, a materials researcher at NASA’s Langley Research Center, in Hampton, Virginia. Brain-protecting diets and medicines, and even the creation of artificial gravity by centrifugation, may also prove necessary.

Hopefully this will be enough to keep astronauts in tiptop mental shape and ready to explore other planets—and without medical repercussions later in life. As a sobering paper in Scientific Reports that was published in July found, the astronauts who ventured to the moon were four times more likely to die from cardiovascular disease than those who remained in orbit within Earth’s protective magnetosphere.

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Chris Drudge is a science writer from Canada. Follow him on Twitter @RosinCerate.

The lead photograph is courtesy of Robert Couse-Baker via Flickr.

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